Comprehensive Physiology Wiley Online Library
For Librarians For Authors Editors About

Integration of Central and Peripheral Regulation of the Circulation during Exercise: Acute and Chronic Adaptations

Patrick J. Mueller, Philip S. Clifford, Craig G. Crandall, Scott A. Smith, Paul J. Fadel 

10.1002/cphy.c160040

Source: Volume 8, Issue 1, January 2018

Published online: December 2017

Full Article on Wiley Online Library



ABSTRACT

Physical movement lasting any more than a few seconds (e.g., exercise), requires coordination of motor control with concomitant changes in the cardiovascular and respiratory support necessary to respond to the rapid increases in metabolic demand. Without such coordination, delivery of oxygen and removal of waste products become rate limiting and will restrict the duration, speed, and quality of movement. Fortunately, under healthy conditions, the central and peripheral nervous systems contribute importantly to this remarkable level of coordination via complex mechanisms that remain to be fully elucidated. The purposes of this review are to present the current state of knowledge regarding: (i) mechanisms by which the body maintains appropriate perfusion pressure to all organs during acute bouts of exercise, and (ii) alterations occurring in these mechanisms via central nervous system adaptations when exercise is performed or not performed on a regular basis (e.g., physically active versus sedentary lifestyle, respectively). Results from studies performed in humans and laboratory animals provide the reader a well‐rounded knowledge base. They are intended to instill an appreciation of what is known, and not known, about how the brain regulates the cardiovascular system during acute bouts of exercise, and the adaptations that occur when individuals exercise regularly versus when chronically sedentary. Discussion of the latter is intended to provide novel mechanisms for the increased incidence of cardiovascular disease in sedentary individuals versus a reduced incidence in individuals who are regularly active. © 2018 American Physiological Society. Compr Physiol 8:103‐151, 2018.

Comprehensive Physiology offers downloadable PowerPoint presentations of figures for non-profit, educational use, provided the content is not modified and full credit is given to the author and publication.

Download a PowerPoint presentation of all images


Figure 1. Figure 1. Direct recordings of arterial pressure, heart rate, and lumbar sympathetic nerve activity (LSNA) at rest and during increasing levels of dynamic exercise in rats. Notice the progressive increase in sympathetic activity related to work rate. RMS = root mean squared Reprinted with permission from DiCarlo et al., 1996 (127).
Figure 2. Figure 2. A schematic representation of the mechanisms mediating the neural cardiovascular adjustments to exercise. Neural signals originating from the brain (central command) and afferent feedback from the aortic and carotid arteries (arterial baroreflex), the heart and lungs (cardiopulmonary baroreflex), and skeletal muscle (exercise pressor reflex) contribute to the intensity‐dependent modulation of sympathetic and parasympathetic nerve activity during exercise. These signals converge centrally within cardiovascular control areas in the medulla oblongata. The ensuing alterations in autonomic outflow mediate changes in heart rate (HR) and contractility as well as the diameter of resistance and capacitance vessels within various tissue beds to modulate cardiac output [HR × stroke volume (SV)] and total vascular conductance (TVC), respectively. These changes then lead to alterations in mean arterial pressure (MAP) appropriate for the intensity and modality of the exercise. Ach, acetylcholine; NA, noradrenaline. Reprinted, with permission, from Fadel and Raven, 2012 (154).
Figure 3. Figure 3. Histograms showing the group mean data (n = 7) of changes in heart rate (HR) (A), systolic blood pressure (SBP) (B) and diastolic blood pressure (DBP) (C) at 0, 30, and 60 s (b15, b45, b75) prior to passive stretch of triceps surae, and in each of the first three respiratory cycles (s1, s2, s3) and at 30 and 60 s during passive stretch performed in young healthy subjects. Mean (± SEM) changes from baseline are shown. These findings indicate that in response to stretch, muscle mechanoreceptors increase heart rate without effect on blood pressure. Thus, mechanically sensitive muscle afferents may contribute to the cardiac acceleration in response to muscle contraction. *P < 0.01. Reprinted, with permission, from Gladwell and Coote, 2002 (179).
Figure 4. Figure 4. Original data from one rat showing a dramatic effect of injecting 10 μg of mechano‐gated channel inhibitor GsMTx4 into the arterial supply of the hindlimb (i.a.) on blood pressure (BP) and heart rate (HR) responses and renal sympathetic nerve activity (RSNA) during the first ∼10 s of tendon stretch. These findings show that inhibition of mechano‐gated Piezo channels reduced the BP, HR, and RSNA responses to tendon stretch indicating a role for these channels in evoking the cardiovascular responses to muscle mechanoreceptor activation. Reprinted, with permission, from Copp SW et al. 2016 (88).
Figure 5. Figure 5. A schematic illustration of the intensity‐dependent resetting of the carotid baroreflex during dynamic exercise. The centering point (CP) is the point at which there is an equal depressor and pressor response to a given change in blood pressure (BP), the operating point (OP) is the prestimulus blood pressure. Both the carotid baroreflex‐heart rate (HR; panel A) and mean arterial pressure (MAP; panel B) stimulus‐response curves progressively reset during exercise in an intensity‐dependent manner without significant changes in maximal gain (sensitivity). A consistent observation for the baroreflex control of HR is the relocation of the OP away from the CP and closer to the threshold of the stimulus‐response curve along with a reduction in the response range as exercise intensity increases (panel A). The relocation of the operating point for HR control positions the baroreflex in a more optimal position to counter hypertensive stimuli with increasing exercise intensity. In contrast, for the carotid baroreflex‐MAP stimulus‐response curve the OP does not relocate away from the centering point and the response range remains the same as at rest with an upward and rightward shift in parallel with an increase in the intensity of exercise (panel B). Reprinted, with permission, from Fadel and Raven, 2012 (154).
Figure 6. Figure 6. Evidence for the contribution of central command to the cardiovascular response to exercise. A and B represent single‐photon‐emission computed tomography (CT) data transferred to images of simultaneously acquired and co‐registered magnetic resonance imaging data. Importantly, computed tomography data represent group averages for the difference between the responses to actual and imaged handgrip exercise. (A) Left: Group CT data for individuals with lower hypnotizability who also reported less perceived effort and demonstrated decreases in brain activation during imagined handgrip exercise relative to actual handgrip exercise. (A) Right: Heart rate data in the lower hypnotizability group showing no change in heart rate to imagined exercise. (B) Left: Group CT data in the higher hypnotizability group who demonstrated similar increases in brain activation during both actual and imaged handgrip exercise and also reported an increase in perceived effort during both actual and imaged handgrip exercise. (B) Right: Group heart rate data in the higher hypnotizability group who demonstrated significant increases in heart rate during imagined exercise (*P < 0.05). The top and bottom of each brain scan represent the anterior and posterior portions of the brain, respectively. White lines indicate brain regions including the insular cortices, thalamic regions (bilaterally), and anterior cingulate cortex. Changes in regional cerebral blood flow distribution were indicated by an arbitrary color range that indicated decreases for the lower hypnotizability group from 5% to 25% (purple to light blue); whereas increases in regional cerebral blood flow distribution ranged from 5% to 25% (green to red) in the higher hypnotizability group. Modified, with permission, from Williamson et al. 2002 (698).
Figure 7. Figure 7. Conceptual framework for the central interaction between arterial baroreceptor and skeletal muscle receptor afferents in the nucleus tractus solitarii (NTS) at rest and during acute bouts of exercise (Ex). (A) Depicts primary baroreceptor afferents forming an excitatory synapse with second order NTS neurons that in turn converge onto an output neuron projecting to nucleus ambiguus (NA) and the caudal ventrolateral medulla (cVLM). The net effect of this NTS circuit is to establish the operating point for heart rate (HR) and central sympathetic nerve activity (SNA) depicted on the baroreflex function curve to the right. (B) In the absence of baroreflex resetting, the model (see right panel) predicts that heightened levels of baroreceptor input during exercise increase NTS output activity. This increases neural activity transmitted to the NA, exciting cardiac vagal motoneurons, and to the cVLM, exciting GABA neurons that inhibit sympathetic premotor neurons in the rostral VLM (rVLM). Activation of these central circuits results in decreased heart rate and sympathoinhibition, respectively (see baroreflex curve on right). Note that the level of neural activity in these pathways is indicated by the relative line thickness. (C) Alternatively, activation of an inhibitory circuit by neural feedback from skeletal muscle [indicated by (I, somatic input)] would normalize the level of NTS output activity and so limit the degree of baroreceptor inhibition of the heart and peripheral vasculature. Activating this inhibitory circuit would reset the arterial baroreflex function curve laterally as indicated by (i) in the right panel. Note that this mechanism is “anatomically” restricted to the caudal NTS. In addition, somatic input would activate sympathoexcitatory neurons in the rVLM, increasing HR and SNA as indicated by (ii) in the right panel. This framework depicts potential central interactions that allow for the resetting of the arterial baroreflex function curve during exercise to allow for maintained baroreflex control in the face of exercise‐induced elevations in HR, SNA, and blood pressure. GABA, γ‐aminobutyric acid; PSNS, parasympathetic nervous system; SNS, sympathetic nervous system. Reprinted, with permission from Potts, 2006 (494).
Figure 8. Figure 8. Schematic diagram depicting a sympathetic nerve fiber and nerve ending in the skeletal muscle vasculature. Norepinephrine (NE) is the primary neurotransmitter and activates α1‐ and α2 adrenergic receptors postsynaptically and α2 adrenergic receptors presynaptically. Adenosine triphosphate (ATP) and neuropeptide Y (NPY) are co‐transmitters. ATP activates G‐protein coupled purinergic receptors (P2X) on smooth muscle cells and ligand gated ion channel purinergic receptors (P2Y) on endothelial cells. NPY activates Y1 receptors on smooth muscle cells. β2 adrenergic and muscarinic (M) receptors do not appear to be activated by post‐ganglionic nerves at rest or during exercise; however β2 adrenergic receptors on smooth muscle cells are activated by circulating epinephrine under various conditions. Muscarinic receptors can be activated by acetylcholine during the defense reaction or under experimental conditions with electrical stimulation of certain brain regions.
Figure 9. Figure 9. Mean arterial pressure, hindlimb blood flow, and hindlimb conductance at onset of exercise with control (saline) and experimental intervention (ganglionic blockade). Data were averaged over 1‐s intervals (except for time 0, which represents a 10‐s average of values obtained while dogs were resting on treadmill). There were no statistically significant differences in conductance responses between the two treatments at 5, 10, and 15 s of exercise. However, conductance values were significantly elevated with ganglionic blockade at 20, 25, and 30 s of exercise (P < 0.01). Reprinted with permission from Buckwalter and Clifford, 1999 (51).
Figure 10. Figure 10. Original record showing a dog proceeding from rest to exercise at 6 mph. At 2 min into exercise, an intra‐arterial bolus of selective alpha1‐antagonist prazosin (0.1 mg) was given. Note the immediate increase in blood flow and conductance in experimental limb, with no changes in systemic blood pressure or blood flow and conductance in control limb. Reprinted with permission from Buckwalter et al., 1997 (58).
Figure 11. Figure 11. A schematic illustration depicting the divergent responses in contracting and inactive skeletal muscle vasculature to increases in muscle sympathetic nerve activity during exercise. The increases in sympathetic outflow are evoked, in large part, via mechanically and metabolically sensitive muscle afferents (the Exercise Pressor Reflex) with further modulation provided via the arterial baroreflex. These intensity‐dependent increases in sympathetic nerve activity cause sympathetically mediated vasoconstriction in inactive muscle, whereas in active muscle there is an attenuation of this sympathetic vasoconstrictor activity. The latter, termed functional sympatholysis, may be attributed to increases in metabolites, muscle temperature, and possibly nitric oxide. This attenuation of sympathetic vasoconstriction in the contracting muscle allows for enhanced muscle blood flow to the metabolically active skeletal muscle. At the same time, the sympathetically mediated vasoconstriction in inactive muscle (and the viscera—not pictured) enhance the redistribution of cardiac output to the contracting skeletal muscles. Collectively, this illustrates the important contributions of the sympathetic nervous system to the matching of muscle blood flow to metabolic demand in exercising muscles.
Figure 12. Figure 12. Graphical illustration of the neural control of skin blood flow in humans. Human cutaneous vasculature is controlled by a sympathetic adrenergic vasoconstrictor limb and a separate sympathetic cholinergic vasodilator limb. Under cool conditions, the vasoconstrictor limb is engaged resulting in reductions in cutaneous vascular conductance and skin blood flow. When internal temperature is elevated, the active vasodilator system is engaged, mediating 85% to 95% of the increase in skin blood flow through increases in cutaneous vascular conductance. The arrow depicts the magnitude of the increases in the respective nerve activities during cooling (increases in sympathetic adrenergic nerve activity) and heating (increases in sympathetic cholinergic nerve activity). Substances within the indicated nerves are the neurotransmitters that have either been shown to, or are proposed to, contribute to the respective responses. NE, norepinephrine; NPY, neuropeptide Y; Ach, acetylcholine; VIP, vasoactive intestinal peptide; PACAP, pituitary adenylate cyclase‐activating peptide; nNO, neuronally derived nitric oxide. Illustration used by permission from Manabu Shibasaki, PhD, Nara Women's University.
Figure 13. Figure 13. Differences in cutaneous vasodilation, expressed as a percentage of preheat stress (i.e., Control) cutaneous vascular conductance, in a subject who was passively heat stressed (Rest—solid circles) and exercise heat stressed (exercise—open circles). Notice the rightward shift of the curve during exercise such that cutaneous vascular conductance is lower at any esophageal temperature during exercise. These finding show that the increase in skin blood flow during exercise‐induced heat stress is delayed relative to passive‐induced heat stress. Figure modified from Kellogg, Johnson, and Kosiba, 1991 (280) with permission.
Figure 14. Figure 14. This figure depicts the linear relationship between increases in cardiac output (Q) and forearm blood flow (FBF, panel A) as well as middle cerebral artery blood velocity (MCAVmean, panel B) at rest (solid circles) and during cycling exercise (EX, open circles). These data suggest that increases in cardiac output contribute to increases in forearm blood flow and brain blood flow during rest and exercise. Reprinted with permission from Ogoh et al., 2005 (465).
Figure 15. Figure 15. Reductions in splanchnic blood flow (Y‐axis expressed in mL/min) during dynamic exercise in patients with mitral valve stenosis (MS), in normal sedentary young men (Sed), and endurance trained athletes (Ath). Data in the left panel are the same as in the right panel, except the right panel is normalized to % maximum oxygen update (%Max VO2). These data demonstrate that as a workload becomes more difficult (i.e., requires more oxygen) there are linear reductions in splanchnic blood flow. Reprinted with permission from Rowell, 1973 (533).
Figure 16. Figure 16. Conceptual diagram of the spectrum of physical activity and proposed influence of positive and negative brain effects on cardiovascular health (positive = green; negative = red). In this context, long term decreases in sympathetic nervous system and increases in parasympathetic nervous system activity produced by an active lifestyle are beneficial as they promote lower resting blood pressures, protection from arrhythmias, and decreased cardiac demand. In contrast, long‐term increases in sympathetic nervous system and decreases in parasympathetic nervous system activity are viewed as detrimental as they are associated with hypertension, arrhythmias, and heart failure. The rapid rise in cardiovascular benefit produced by being physically active reflects epidemiological evidence from Blair and colleagues whose data indicate that the largest relative health benefit is derived in individuals moving from the lowest quintile (i.e., 1 of 5) of fitness category to only the second lowest quintile of cardiorespiratory fitness. The diagram also allows for shifts in the curve to the right or left due to genetics, preexisting conditions, or other factors that predispose or influence individuals to more positive (green block arrow) or negative (red block arrow) cardiovascular health.
Figure 17. Figure 17. Schematic diagram illustrating the role of important neural pathways involved in integration and generation of sympathetic vasoconstrictor outflow. Under healthy conditions, which include regular physical activity, all pathways actively regulate sympathetic outflow to the vasculature, particularly during bouts of exercise. At rest, the rostral ventrolateral medulla (RVLM) serves as the primary site of sympathetic outflow and its activity is limited by inhibitory inputs (dotted lines) from the caudal ventrolateral medulla (CVLM). The CVLM provides inhibition due to inputs driven in part by the nucleus tractus solitarius (NTS). Even at rest, the NTS is tonically active due to input from arterial baroreceptors but can also be influenced by inputs from contracting muscle during exercise. “Central command” neurons in higher centers of the brain initiate movement and influence pathways that alter sympathetic outflow via projections to PVN and NTS. Under sedentary conditions (red arrows and dotted circles), there is a lack of activation of pathways produced by regular bouts of exercise and likely produces alterations in neuronal function, that is, neuroplasticity, which result in increased sympathetic outflow to the vasculature. Modified from Mueller, 2010 (422) with permission.
Figure 18. Figure 18. Schematic diagram illustrating the role of important neural pathways involved in the integration and generation of sympathetic and parasympathetic outflow to the heart. As with control of tonic sympathetic vasoconstrictor activity, physically active conditions result in all pathways actively regulating sympathetic outflow to the heart, particularly during periodic bouts of exercise. At rest, the nucleus ambiguus (NA), and in some species, the dorsal motor nucleus of the vagus (DMV), serve as the primary site(s) of parasympathetic outflow to the heart. Activity of the NA and DMV are driven by excitatory inputs (solid lines, plus signs) from nucleus tractus solitarius (NTS). Even at rest, the NTS is tonically active due to input from arterial baroreceptors and maintains ongoing parasympathetic nerve activity (PNA, i.e., vagal tone) to suppress baseline heart rate (HR) well below its intrinsic rate. Brain regions controlling sympathetic nerve activity (SNA) to the heart appear more complex (some not shown) but are least active at rest and typically only become active after PNA withdrawal during exercise. Under sedentary conditions (red arrows and dotted circles), there is a lack of activation of pathways produced by regular bouts of exercise and likely produces alterations in neuronal function, that is, neuroplasticity, which result in decreased PNA and increased SNA to the heart, raising resting HR. Changes in contractility may depend on whether increased SNA produces compensatory increases or over time induces decreases as a result of heart failure. Modified from Mueller, 2010 (422) with permission.


Figure 1. Direct recordings of arterial pressure, heart rate, and lumbar sympathetic nerve activity (LSNA) at rest and during increasing levels of dynamic exercise in rats. Notice the progressive increase in sympathetic activity related to work rate. RMS = root mean squared Reprinted with permission from DiCarlo et al., 1996 (127).


Figure 2. A schematic representation of the mechanisms mediating the neural cardiovascular adjustments to exercise. Neural signals originating from the brain (central command) and afferent feedback from the aortic and carotid arteries (arterial baroreflex), the heart and lungs (cardiopulmonary baroreflex), and skeletal muscle (exercise pressor reflex) contribute to the intensity‐dependent modulation of sympathetic and parasympathetic nerve activity during exercise. These signals converge centrally within cardiovascular control areas in the medulla oblongata. The ensuing alterations in autonomic outflow mediate changes in heart rate (HR) and contractility as well as the diameter of resistance and capacitance vessels within various tissue beds to modulate cardiac output [HR × stroke volume (SV)] and total vascular conductance (TVC), respectively. These changes then lead to alterations in mean arterial pressure (MAP) appropriate for the intensity and modality of the exercise. Ach, acetylcholine; NA, noradrenaline. Reprinted, with permission, from Fadel and Raven, 2012 (154).


Figure 3. Histograms showing the group mean data (n = 7) of changes in heart rate (HR) (A), systolic blood pressure (SBP) (B) and diastolic blood pressure (DBP) (C) at 0, 30, and 60 s (b15, b45, b75) prior to passive stretch of triceps surae, and in each of the first three respiratory cycles (s1, s2, s3) and at 30 and 60 s during passive stretch performed in young healthy subjects. Mean (± SEM) changes from baseline are shown. These findings indicate that in response to stretch, muscle mechanoreceptors increase heart rate without effect on blood pressure. Thus, mechanically sensitive muscle afferents may contribute to the cardiac acceleration in response to muscle contraction. *P < 0.01. Reprinted, with permission, from Gladwell and Coote, 2002 (179).


Figure 4. Original data from one rat showing a dramatic effect of injecting 10 μg of mechano‐gated channel inhibitor GsMTx4 into the arterial supply of the hindlimb (i.a.) on blood pressure (BP) and heart rate (HR) responses and renal sympathetic nerve activity (RSNA) during the first ∼10 s of tendon stretch. These findings show that inhibition of mechano‐gated Piezo channels reduced the BP, HR, and RSNA responses to tendon stretch indicating a role for these channels in evoking the cardiovascular responses to muscle mechanoreceptor activation. Reprinted, with permission, from Copp SW et al. 2016 (88).


Figure 5. A schematic illustration of the intensity‐dependent resetting of the carotid baroreflex during dynamic exercise. The centering point (CP) is the point at which there is an equal depressor and pressor response to a given change in blood pressure (BP), the operating point (OP) is the prestimulus blood pressure. Both the carotid baroreflex‐heart rate (HR; panel A) and mean arterial pressure (MAP; panel B) stimulus‐response curves progressively reset during exercise in an intensity‐dependent manner without significant changes in maximal gain (sensitivity). A consistent observation for the baroreflex control of HR is the relocation of the OP away from the CP and closer to the threshold of the stimulus‐response curve along with a reduction in the response range as exercise intensity increases (panel A). The relocation of the operating point for HR control positions the baroreflex in a more optimal position to counter hypertensive stimuli with increasing exercise intensity. In contrast, for the carotid baroreflex‐MAP stimulus‐response curve the OP does not relocate away from the centering point and the response range remains the same as at rest with an upward and rightward shift in parallel with an increase in the intensity of exercise (panel B). Reprinted, with permission, from Fadel and Raven, 2012 (154).


Figure 6. Evidence for the contribution of central command to the cardiovascular response to exercise. A and B represent single‐photon‐emission computed tomography (CT) data transferred to images of simultaneously acquired and co‐registered magnetic resonance imaging data. Importantly, computed tomography data represent group averages for the difference between the responses to actual and imaged handgrip exercise. (A) Left: Group CT data for individuals with lower hypnotizability who also reported less perceived effort and demonstrated decreases in brain activation during imagined handgrip exercise relative to actual handgrip exercise. (A) Right: Heart rate data in the lower hypnotizability group showing no change in heart rate to imagined exercise. (B) Left: Group CT data in the higher hypnotizability group who demonstrated similar increases in brain activation during both actual and imaged handgrip exercise and also reported an increase in perceived effort during both actual and imaged handgrip exercise. (B) Right: Group heart rate data in the higher hypnotizability group who demonstrated significant increases in heart rate during imagined exercise (*P < 0.05). The top and bottom of each brain scan represent the anterior and posterior portions of the brain, respectively. White lines indicate brain regions including the insular cortices, thalamic regions (bilaterally), and anterior cingulate cortex. Changes in regional cerebral blood flow distribution were indicated by an arbitrary color range that indicated decreases for the lower hypnotizability group from 5% to 25% (purple to light blue); whereas increases in regional cerebral blood flow distribution ranged from 5% to 25% (green to red) in the higher hypnotizability group. Modified, with permission, from Williamson et al. 2002 (698).


Figure 7. Conceptual framework for the central interaction between arterial baroreceptor and skeletal muscle receptor afferents in the nucleus tractus solitarii (NTS) at rest and during acute bouts of exercise (Ex). (A) Depicts primary baroreceptor afferents forming an excitatory synapse with second order NTS neurons that in turn converge onto an output neuron projecting to nucleus ambiguus (NA) and the caudal ventrolateral medulla (cVLM). The net effect of this NTS circuit is to establish the operating point for heart rate (HR) and central sympathetic nerve activity (SNA) depicted on the baroreflex function curve to the right. (B) In the absence of baroreflex resetting, the model (see right panel) predicts that heightened levels of baroreceptor input during exercise increase NTS output activity. This increases neural activity transmitted to the NA, exciting cardiac vagal motoneurons, and to the cVLM, exciting GABA neurons that inhibit sympathetic premotor neurons in the rostral VLM (rVLM). Activation of these central circuits results in decreased heart rate and sympathoinhibition, respectively (see baroreflex curve on right). Note that the level of neural activity in these pathways is indicated by the relative line thickness. (C) Alternatively, activation of an inhibitory circuit by neural feedback from skeletal muscle [indicated by (I, somatic input)] would normalize the level of NTS output activity and so limit the degree of baroreceptor inhibition of the heart and peripheral vasculature. Activating this inhibitory circuit would reset the arterial baroreflex function curve laterally as indicated by (i) in the right panel. Note that this mechanism is “anatomically” restricted to the caudal NTS. In addition, somatic input would activate sympathoexcitatory neurons in the rVLM, increasing HR and SNA as indicated by (ii) in the right panel. This framework depicts potential central interactions that allow for the resetting of the arterial baroreflex function curve during exercise to allow for maintained baroreflex control in the face of exercise‐induced elevations in HR, SNA, and blood pressure. GABA, γ‐aminobutyric acid; PSNS, parasympathetic nervous system; SNS, sympathetic nervous system. Reprinted, with permission from Potts, 2006 (494).


Figure 8. Schematic diagram depicting a sympathetic nerve fiber and nerve ending in the skeletal muscle vasculature. Norepinephrine (NE) is the primary neurotransmitter and activates α1‐ and α2 adrenergic receptors postsynaptically and α2 adrenergic receptors presynaptically. Adenosine triphosphate (ATP) and neuropeptide Y (NPY) are co‐transmitters. ATP activates G‐protein coupled purinergic receptors (P2X) on smooth muscle cells and ligand gated ion channel purinergic receptors (P2Y) on endothelial cells. NPY activates Y1 receptors on smooth muscle cells. β2 adrenergic and muscarinic (M) receptors do not appear to be activated by post‐ganglionic nerves at rest or during exercise; however β2 adrenergic receptors on smooth muscle cells are activated by circulating epinephrine under various conditions. Muscarinic receptors can be activated by acetylcholine during the defense reaction or under experimental conditions with electrical stimulation of certain brain regions.


Figure 9. Mean arterial pressure, hindlimb blood flow, and hindlimb conductance at onset of exercise with control (saline) and experimental intervention (ganglionic blockade). Data were averaged over 1‐s intervals (except for time 0, which represents a 10‐s average of values obtained while dogs were resting on treadmill). There were no statistically significant differences in conductance responses between the two treatments at 5, 10, and 15 s of exercise. However, conductance values were significantly elevated with ganglionic blockade at 20, 25, and 30 s of exercise (P < 0.01). Reprinted with permission from Buckwalter and Clifford, 1999 (51).


Figure 10. Original record showing a dog proceeding from rest to exercise at 6 mph. At 2 min into exercise, an intra‐arterial bolus of selective alpha1‐antagonist prazosin (0.1 mg) was given. Note the immediate increase in blood flow and conductance in experimental limb, with no changes in systemic blood pressure or blood flow and conductance in control limb. Reprinted with permission from Buckwalter et al., 1997 (58).


Figure 11. A schematic illustration depicting the divergent responses in contracting and inactive skeletal muscle vasculature to increases in muscle sympathetic nerve activity during exercise. The increases in sympathetic outflow are evoked, in large part, via mechanically and metabolically sensitive muscle afferents (the Exercise Pressor Reflex) with further modulation provided via the arterial baroreflex. These intensity‐dependent increases in sympathetic nerve activity cause sympathetically mediated vasoconstriction in inactive muscle, whereas in active muscle there is an attenuation of this sympathetic vasoconstrictor activity. The latter, termed functional sympatholysis, may be attributed to increases in metabolites, muscle temperature, and possibly nitric oxide. This attenuation of sympathetic vasoconstriction in the contracting muscle allows for enhanced muscle blood flow to the metabolically active skeletal muscle. At the same time, the sympathetically mediated vasoconstriction in inactive muscle (and the viscera—not pictured) enhance the redistribution of cardiac output to the contracting skeletal muscles. Collectively, this illustrates the important contributions of the sympathetic nervous system to the matching of muscle blood flow to metabolic demand in exercising muscles.


Figure 12. Graphical illustration of the neural control of skin blood flow in humans. Human cutaneous vasculature is controlled by a sympathetic adrenergic vasoconstrictor limb and a separate sympathetic cholinergic vasodilator limb. Under cool conditions, the vasoconstrictor limb is engaged resulting in reductions in cutaneous vascular conductance and skin blood flow. When internal temperature is elevated, the active vasodilator system is engaged, mediating 85% to 95% of the increase in skin blood flow through increases in cutaneous vascular conductance. The arrow depicts the magnitude of the increases in the respective nerve activities during cooling (increases in sympathetic adrenergic nerve activity) and heating (increases in sympathetic cholinergic nerve activity). Substances within the indicated nerves are the neurotransmitters that have either been shown to, or are proposed to, contribute to the respective responses. NE, norepinephrine; NPY, neuropeptide Y; Ach, acetylcholine; VIP, vasoactive intestinal peptide; PACAP, pituitary adenylate cyclase‐activating peptide; nNO, neuronally derived nitric oxide. Illustration used by permission from Manabu Shibasaki, PhD, Nara Women's University.


Figure 13. Differences in cutaneous vasodilation, expressed as a percentage of preheat stress (i.e., Control) cutaneous vascular conductance, in a subject who was passively heat stressed (Rest—solid circles) and exercise heat stressed (exercise—open circles). Notice the rightward shift of the curve during exercise such that cutaneous vascular conductance is lower at any esophageal temperature during exercise. These finding show that the increase in skin blood flow during exercise‐induced heat stress is delayed relative to passive‐induced heat stress. Figure modified from Kellogg, Johnson, and Kosiba, 1991 (280) with permission.


Figure 14. This figure depicts the linear relationship between increases in cardiac output (Q) and forearm blood flow (FBF, panel A) as well as middle cerebral artery blood velocity (MCAVmean, panel B) at rest (solid circles) and during cycling exercise (EX, open circles). These data suggest that increases in cardiac output contribute to increases in forearm blood flow and brain blood flow during rest and exercise. Reprinted with permission from Ogoh et al., 2005 (465).


Figure 15. Reductions in splanchnic blood flow (Y‐axis expressed in mL/min) during dynamic exercise in patients with mitral valve stenosis (MS), in normal sedentary young men (Sed), and endurance trained athletes (Ath). Data in the left panel are the same as in the right panel, except the right panel is normalized to % maximum oxygen update (%Max VO2). These data demonstrate that as a workload becomes more difficult (i.e., requires more oxygen) there are linear reductions in splanchnic blood flow. Reprinted with permission from Rowell, 1973 (533).


Figure 16. Conceptual diagram of the spectrum of physical activity and proposed influence of positive and negative brain effects on cardiovascular health (positive = green; negative = red). In this context, long term decreases in sympathetic nervous system and increases in parasympathetic nervous system activity produced by an active lifestyle are beneficial as they promote lower resting blood pressures, protection from arrhythmias, and decreased cardiac demand. In contrast, long‐term increases in sympathetic nervous system and decreases in parasympathetic nervous system activity are viewed as detrimental as they are associated with hypertension, arrhythmias, and heart failure. The rapid rise in cardiovascular benefit produced by being physically active reflects epidemiological evidence from Blair and colleagues whose data indicate that the largest relative health benefit is derived in individuals moving from the lowest quintile (i.e., 1 of 5) of fitness category to only the second lowest quintile of cardiorespiratory fitness. The diagram also allows for shifts in the curve to the right or left due to genetics, preexisting conditions, or other factors that predispose or influence individuals to more positive (green block arrow) or negative (red block arrow) cardiovascular health.


Figure 17. Schematic diagram illustrating the role of important neural pathways involved in integration and generation of sympathetic vasoconstrictor outflow. Under healthy conditions, which include regular physical activity, all pathways actively regulate sympathetic outflow to the vasculature, particularly during bouts of exercise. At rest, the rostral ventrolateral medulla (RVLM) serves as the primary site of sympathetic outflow and its activity is limited by inhibitory inputs (dotted lines) from the caudal ventrolateral medulla (CVLM). The CVLM provides inhibition due to inputs driven in part by the nucleus tractus solitarius (NTS). Even at rest, the NTS is tonically active due to input from arterial baroreceptors but can also be influenced by inputs from contracting muscle during exercise. “Central command” neurons in higher centers of the brain initiate movement and influence pathways that alter sympathetic outflow via projections to PVN and NTS. Under sedentary conditions (red arrows and dotted circles), there is a lack of activation of pathways produced by regular bouts of exercise and likely produces alterations in neuronal function, that is, neuroplasticity, which result in increased sympathetic outflow to the vasculature. Modified from Mueller, 2010 (422) with permission.


Figure 18. Schematic diagram illustrating the role of important neural pathways involved in the integration and generation of sympathetic and parasympathetic outflow to the heart. As with control of tonic sympathetic vasoconstrictor activity, physically active conditions result in all pathways actively regulating sympathetic outflow to the heart, particularly during periodic bouts of exercise. At rest, the nucleus ambiguus (NA), and in some species, the dorsal motor nucleus of the vagus (DMV), serve as the primary site(s) of parasympathetic outflow to the heart. Activity of the NA and DMV are driven by excitatory inputs (solid lines, plus signs) from nucleus tractus solitarius (NTS). Even at rest, the NTS is tonically active due to input from arterial baroreceptors and maintains ongoing parasympathetic nerve activity (PNA, i.e., vagal tone) to suppress baseline heart rate (HR) well below its intrinsic rate. Brain regions controlling sympathetic nerve activity (SNA) to the heart appear more complex (some not shown) but are least active at rest and typically only become active after PNA withdrawal during exercise. Under sedentary conditions (red arrows and dotted circles), there is a lack of activation of pathways produced by regular bouts of exercise and likely produces alterations in neuronal function, that is, neuroplasticity, which result in decreased PNA and increased SNA to the heart, raising resting HR. Changes in contractility may depend on whether increased SNA produces compensatory increases or over time induces decreases as a result of heart failure. Modified from Mueller, 2010 (422) with permission.
References
 1.Abrahams VC, Hilton SM, Zbrozyna A. Active muscle vasodilatation produced by stimulation of the brain stem: Its significance in the defence reaction. J Physiol 154: 491‐513, 1960.
 2.Ahlborg G, Juhlin‐Dannfelt A. Effect of beta‐receptor blockade on splanchnic and muscle metabolism during prolonged exercise in men. J Appl Physiol 76: 1037‐1042, 1994.
 3.Aicher SA, Randich A. Antinociception and cardiovascular responses produced by electrical stimulation in the nucleus tractus solitarius, nucleus reticularis ventralis, and the caudal medulla. Pain 42: 103‐119, 1990.
 4.Al‐Khazraji BK, Saleem A, Goldman D, Jackson DN. From one generation to the next: A comprehensive account of sympathetic receptor control in branching arteriolar trees. J Physiol 593: 3093‐3108, 2015.
 5.Alam M, Smirk FH. Observation in man upon a blood pressure raising reflex arising from voluntary muscles. J Physiol 89: 372‐383, 1937.
 6.Ally A. Ventrolateral medullary control of cardiovascular activity during muscle contraction. Neurosci Biobehav Rev 23: 65‐86, 1998.
 7.Amann M, Sidhu SK, Weavil JC, Mangum TS, Venturelli M. Autonomic responses to exercise: Group III/IV muscle afferents and fatigue. Auto Neurosci 188: 19‐23, 2015.
 8.Andersen P, Saltin B. Maximal perfusion of skeletal muscle in man. J Physiol, Lond 366: 233‐249, 1985.
 9.Anderson KM, Faber JE. Differential sensitivity of arteriolar alpha 1‐ and alpha 2‐adrenoceptor constriction to metabolic inhibition during rat skeletal muscle contraction. Circ Res 69: 174‐184, 1991.
 10.Andres KH, von During M, Schmidt RF. Sensory innervation of the Achilles tendon by group III and IV afferent fibers. Anat Embryol (Berl) 172: 145‐156, 1985.
 11.Andresen MC, Kunze DL. Nucleus tractus solitarius–‐gateway to neural circulatory control. Annu Rev Physiol 56: 93‐116, 1994.
 12.Armstrong RB, Laughlin MH. Atropine: No effect on exercise muscle hyperemia in conscious rats. J Appl Physiol 61: 679‐682, 1986.
 13.Arrowood J, Mohany P, McNamara C, Thames M. Cardiopulmonary reflexes do not modulate exercise pressor reflexes during isometric exercise in humans. J Appl Physiol 74: 2559‐2565, 1993.
 14.Baily TW, Jin Y‐H, Doyle MW, Smith SM, Andresen MC. Vasopressin inhibits glutamate release via two distinct modes in the brainstem. J Neurosci 26: 6131‐6142, 2006.
 15.Barcroft H, Bonnar WM, Edholm OG, Effron AS. On sympathetic vasoconstrictor tone in human skeletal muscle. J Physiol 102: 21‐31, 1943.
 16.Barman S. Descending projections of hypothalamic neurons with sympathetic nerve‐related activity. J Neurophysiol 64: 1019‐1032, 1990.
 17.Basnayake SD, Hyam JA, Pereira EA, Schweder PM, Brittain JS, Aziz TZ, Green AL, Paterson DJ. Identifying cardiovascular neurocircuitry involved in the exercise pressor reflex in humans using functional neurosurgery. J Appl Physiol 110: 881‐891, 2011.
 18.Bauer RM, Iwamoto GA, Waldrop TG. Ventrolateral medullary neurons modulate pressor reflex to muscular contraction. Am J Physiol 257: R1154‐R1161, 1989.
 19.Baum K, Selle K, Leyk D, Essfeld D. Comparison of blood pressure and heart rate responses to isometric exercise and passive muscle stretch in humans. Eur J Appl Physiol Occup Physiol 70: 240‐245, 1995.
 20.Beatty JA, Kramer JM, Plowey ED, Waldrop TG. Physical exercise decreases neuronal activity in the posterior hypothalamic area of spontaneously hypertensive rats. J Appl Physiol 98: 572‐578, 2005.
 21.Beaty O, Donald DE. Role of potassium in the transient reduction of vasoconstrictive responses of muscle resistance vessels during rhythmic exercise in dogs. Circ Research 41: 452‐460, 1977.
 22.Becker LK, Santos RAS, Campagnole‐Santos MJ. Cardiovascular effects of angiotensin II and angiotensin‐(1‐7) at the RVLM of trained normotensive rats. Brain Res 1040: 121‐128, 2005.
 23.Bedford T, Loi P, Crandall C. A model of dynamic exericse—the decerebrate rat locomotor preparation. J Appl Physiol 72: 121‐127, 1992.
 24.Bevegard BS, Shepherd JT. Circulatory effects of stimulating the carotid arterial stretch receptors in man at rest and during exercise. J Clin Invest 45: 132‐142, 1966.
 25.Bevegard S, Castenfors J, Lindblad L. Effect of carotid sinus stimulation on cardiac output and peripheral vasular resistance during changes in blood volume distribution in man. Acta Physiol Scand 101: 50‐57, 1977.
 26.Bevegard S, Castenfors J, Lindblad LE, Tranesjo TJ. Blood pressure and heart rate regulating capacity of the carotid sinus during changes in blood volume distribution in man. Acta Physiol Scand 99: 300‐312, 1977.
 27.Bill A, Linder J. Sympathetic control of cerebral blood flow in acute arterial hypertension. Acta Physiol Scand 96: 114‐121, 1976.
 28.Bini G, Hagbarth KE, Hynninen P, Wallin BG. Thermoregulatory and rhythm‐generating mechanisms governing the sudomotor and vasoconstrictor outflow in human cutaneous nerves. J Physiol 306: 537‐552, 1980.
 29.Blair DA, Glover WE, Kidd BSL, Roddie IC. Peripheral vascular effects of bretylium tosylate in man. Br J Pharmacol 15: 466‐475, 1960.
 30.Bleys RL, Cowen T. Innervation of cerebral blood vessels: morphology, plasticity, age‐related, and Alzheimer's disease‐related neurodegeneration. Microsc Res Tech 53: 106‐118, 2001.
 31.Bolme P, Novotny J. Conditional reflex activation of sympathetic cholinergic vasodilator nerves in the dog. Acta Physiol Scand 77: 58‐67, 1969.
 32.Bolme P, Novotny J, Uvnas B, Wright PG. Species distribution of sympathetic cholinergic vasodilator nerves in skeletal muscle. Acta Physiol Scand 78: 60‐64, 1970.
 33.Booth FW, Lees SJ. Physically active subjects should be the control group. Med Sci Sports Exerc 38: 405‐406, 2006.
 34.Boscan P, Kasparov S, Paton JF. Somatic nociception activates NK1 receptors in the nucleus tractus solitarii to attenuate the baroreceptor cardiac reflex. Eur J Neurosci 16: 907‐920, 2002.
 35.Boscan P, Pickering AE, Paton JF. The nucleus of the solitary tract: An integrating station for nociceptive and cardiorespiratory afferents. Exp Physiol 87: 259‐266, 2002.
 36.Bouchama A, Knochel JP. Heat stroke. N Engl J Med 346: 1978‐1988, 2002.
 37.Boulton D, Taylor CE, Macefield VG, Green S. Contributions of central command and muscle feedback to sympathetic nerve activity in contracting human skeletal muscle. Front Physiol 7: 163, 2016.
 38.Boura ALA, Green. AF. The actions of bretylium: Adrenergic neurone blocking and other effects. Brit J Pharmacol 14: 536–548, 1959.
 39.Bradbury EJ, Burnstock G, McMahon SB. The expression of P2X3 purinoreceptors in sensory neurons: Effects of axotomy and glial‐derived neurotrophic factor. Mol Cell Neurosci 12: 256‐268, 1998.
 40.Bradley E, Law A, Bell D, Johnson CD. Effects of varying impulse number on cotransmitter contributions to sympathetic vasoconstriction in rat tail artery. Am J Physiol Heart Circ Physiol 284: H2007‐H2014, 2003.
 41.Bradley SE, Childs AW, Combes B, Cournand A, Wade OL, Wheeler HO. The effect of exercise on the splanchnic blood flow and splanchnic blood volume in normal man. Clin Sci (Lond) 15: 457‐463, 1956.
 42.Brengelmann GL, Freund PR, Rowell LB, Olerud JE, Kraning KK. Absence of active vasodilation associated with congenital absence of sweat glands in humans. Am J Physiol 240: H571‐H575, 1981.
 43.Brengelmann GL, Johnson JM, Hermansen L, Rowell LB. Altered control of skin blood flow during exercise at high internal temperatures. J Appl Physiol 43: 790‐794, 1977.
 44.Brengelmann GL, Savage MV. Temperature regulation in the neutral zone. Ann N Y Acad Sci 813: 39‐50, 1997.
 45.Brock RW, Tschakovsky ME, Shoemaker JK, Halliwill JR, Joyner MJ, Hughson RL. Effects of acetylcholine and nitric oxide on forearm blood flow at rest and after a single muscle contraction. J Appl Physiol 85: 2249‐2254, 1998.
 46.Brodin E, Linderoth B, Gazelius B, Ungerstedt U. In vivo release of substance P in cat dorsal horn studied with microdialysis. Neurosci Lett 76: 357‐362, 1987.
 47.Brothers RM, Haslund ML, Wray DW, Raven PB, Sander M. Exercise‐induced inhibition of angiotensin II vasoconstriction in human thigh muscle. J Physiol 577: 727‐737, 2006.
 48.Brum PC, Da Silva GJJ, Moreira ED, Ida F, Negrao CE, Krieger EM. Exercise training increases baroreceptor gain sensitivity in normal and hypertensive rats. Hypertension 36: 1018‐1022, 2000.
 49.Brunner MJ, Greene AS, Frankle AE, Shoukas AA. Carotid sinus baroreceptor control of splanchnic resistance and capacity. Am J Physiol 255: H1305‐H1310, 1988.
 50.Buckwalter JB, Clifford PS. Alpha‐adrenergic vasoconstriction in active skeletal muscles during dynamic exercise. Am J Physiol Heart Circ Physiol 277: H33‐H39, 1999.
 51.Buckwalter JB, Clifford PS. Autonomic control of skeletal muscle blood flow at the onset of exercise. Am J Physiol 277: 1872‐1877, 1999.
 52.Buckwalter JB, Clifford PS. The paradox of sympathetic vasoconstriction in exercising skeletal muscle. Exerc Sport Sci Rev 29: 159‐163, 2001.
 53.Buckwalter JB, Hamann JJ, Clifford PS. Neuropeptide Y1 receptor vasoconstriction in exercising canine skeletal muscles. J Appl Physiol 99: 2115‐2120, 2005.
 54.Buckwalter JB, Hamann JJ, Clifford PS. Vasoconstriction in active skeletal muscles: A potential role for P2X purinergic receptors? J Appl Physiol 95: 953‐959, 2003.
 55.Buckwalter JB, Hamann JJ, Kluess HA, Clifford PS. Vasoconstriction in exercising skeletal muscles: A potential role for neuropeptide Y? Am J Physiol Heart Circ Physiol 287: H144‐H149, 2004.
 56.Buckwalter JB, Mueller PJ, Clifford PS. alpha1‐adrenergic‐receptor responsiveness in skeletal muscle during dynamic exercise. J Appl Physiol 85: 2277‐2283, 1998.
 57.Buckwalter JB, Mueller PJ, Clifford PS. Autonomic control of skeletal muscle vasodilation during exercise. J Appl Physiol 83: 2037‐2042, 1997.
 58.Buckwalter JB, Mueller PJ, Clifford PS. Sympathetic vasoconstriction in active skeletal muscles during dynamic exercise. J Appl Physiol 83: 1575‐1580, 1997.
 59.Buckwalter JB, Naik JS, Valic Z, Clifford PS. Exercise attenuates alpha‐adrenergic‐receptor responsiveness in skeletal muscle vasculature. J Appl Physiol 90: 172‐178, 2001.
 60.Buckwalter JB, Ruble SB, Mueller PJ, Clifford PS. Skeletal muscle vasodilation at the onset of exercise. J Appl Physiol 85: 1649‐1654, 1998.
 61.Buckwalter JB, Taylor JC, Hamann JJ, Clifford PS. Do P2X purinergic receptors regulate skeletal muscle blood flow during exercise? Am J Physiol Heart Circ Physiol 286: H633‐H639, 2004.
 62.Buckwalter JB, Taylor JC, Hamann JJ, Clifford PS. Role of nitric oxide in exercise sympatholysis. J Appl Physiol 97: 417‐423, 2004.
 63.Buono MJ, Sjoholm NT. Effect of physical training on peripheral sweat production. J Appl Physiol 65: 811‐814, 1988.
 64.Burcher E, Garlick D. Antagonism of vasoconstrictor responses by exercise in the gracilis muscle of the dog. J Pharmacol Exp Ther 187: 78‐85, 1973.
 65.Burnstock G. P2 purinoceptors: Historical perspective and classification. Ciba Found Symp 198: 1‐13, 1996.
 66.Burnstock G, Kennedy C. Is there a basis for distinguishing two types of P2‐purinoceptor? Gen Pharmacol 16: 433‐440, 1985.
 67.Bylund DB, Regan JW, Faber JE, Hieble JP, Triggle CR, Ruffolo RR. Vascular alpha‐adrenoceptors: From the gene to the human. Can J Physiol Pharmacol 73: 533‐543, 1995.
 68.Campagnole‐Santos MJ, Diz DI, Ferrario CM. Baroreceptor reflex modulation by angiotensin II at the nucleus tractus solitarii. Hypertension 11: I167‐I171, 1988.
 69.Carter R, III, Watenpaugh DE, Wasmund WL, Wasmund SL, Smith ML. Muscle pump and central command during recovery from exercise in humans. J Appl Physiol 87: 1463‐1469., 1999.
 70.Cechetto DF, Saper CB. Role of the Cerebral Cortex in Autonomic Function. Central Regulation of Autonomic Function. New York, NY: Oxford University Press, 1990, pp. 208‐223.
 71.Chaiyakul P, Reidman D, Pilipovic L, Maher T, Ally A. Further evidence that extracellular serotonin in the rostral ventrolateral medulla modulates 5‐HT1A receptor‐mediated attenuation of exercise pressor reflex. Brain Res 900: 186‐194, 2001.
 72.Charkoudian N. Mechanisms and modifiers of reflex induced cutaneous vasodilation and vasoconstriction in humans. J Appl Physiol 109: 1221‐1228, 2010.
 73.Charkoudian N. Skin blood flow in adult human thermoregulation: How it works, when it does not, and why. Mayo Clin Proc 78: 603‐612, 2003.
 74.Chavoshan B, Sander M, Sybert TE, Hansen J, Victor RG, Thomas GD. Nitric oxide‐dependent modulation of sympathetic neural control of oxygenation in exercising human skeletal muscle. J Physiol 540: 377‐386, 2002.
 75.Chen CC, Akopian AN, Sivilotti L, Colquhoun D, Burnstock G, Wood JN. A P2X purinoceptor expressed by a subset of sensory neurons. Nature 377: 428‐431, 1995.
 76.Chotani MA, Flavahan S, Mitra S, Daunt D, Flavahan NA. Silent alpha(2C)‐adrenergic receptors enable cold‐induced vasoconstriction in cutaneous arteries. Am J Physiol Heart Circ Physiol 278: H1075‐H1083, 2000.
 77.Christensen NJ, Galbo H. Sympathetic nervous activity during exercise. Ann Rev Physiol 45: 139‐153, 1983.
 78.Ciriello J, Calaresu FR. Lateral reticular nucleus: A site of somatic and cardiovascular integration in the cat. Am J Physiol 233: R100‐R109, 1977.
 79.Ciriello J, Hochstenbach SL, Roder S. Central projections of baroreceptor and chemoreceptor afferent fibers in the rat. In: Barraco IRA, editor. The Nucleus of the Solitary Tract. Boca Raton, FL: CRC, 1994, pp. 35‐50.
 80.Clifford PS, Hamann JJ, Valic Z, Buckwalter JB. Point‐Counterpoint: The muscle pump is not an important determinant of muscle blood flow during exercise. J Appl Physiol 99: 371‐375, 2005.
 81.Collins H, DiCarlo S. Cardiac afferents attenuate the muscle metaboreflex in the rat. J Appl Physiol 75: 114‐120, 1993.
 82.Collins HL, Augustyniak RA, Ansorge EJ, O'Leary DS. Carotid baroreflex pressor responses at rest and during exercise: Cardiac output vs. regional vasoconstriction. Am J Physiol Heart Circ Physiol 280: H642‐H648, 2001.
 83.Collins HL, Rodenbaugh DW, DiCarlo SE. Daily exercise attenuated the sympathetic component of the spontaneous arterial baroreflex control of heart rate in hypertensive rats. Clin Exper Hypertens 22: 607‐622, 2000.
 84.Collins HL, Rodenbaugh DW, DiCarlo SE. Daily exercise attenuates the development of arterial blood pressure related cardiovascular risk factors in hypertensive rats. Clin Exper Hypertens 22: 193‐202, 2000.
 85.Cooke JP, Shepherd JT, Vanhoutte PM. The effect of warming on adrenergic neurotransmission in canine cutaneous vein. Circ Res 54: 547‐553, 1984.
 86.Coote JH. A role for the paraventricular nucleus of the hypothalamus in the autonomic control of heart and kidney. Exp Physiol 90: 169‐173, 2005.
 87.Coote JH, Hilton SM, Perez‐Gonzalez JF. The reflex nature of the pressor response to muscular exercise. J Physiol (Lond) 214: 789‐804, 1971.
 88.Copp SW, Kim JS, Ruiz‐Velasco V, Kaufman MP. The mechano‐gated channel inhibitor GsMTx4 reduces the exercise pressor reflex in decebrate rats. J Physiol 594.3: 641‐655, 2016.
 89.Corcondilas A, Koroxenidis GT, Shepherd JT. Effect of a brief contraction of forearm muscles on forearm blood flow. J Appl Physiol 19: 142‐146, 1964.
 90.Corfield DR, Murphy K, Josephs O, Fink GR, Frackowiak RSJ, Guz A, Adams L, Turner R. Cortical and subcortical control of tongue movement in humans: A functional neuroimaging study using fMRI. J Appl Physiol 86: 1468‐1477, 1999.
 91.Cornelissen VA, Fagard RH. Effects of endurance training on blood pressure, blood pressure‐regulating mechanisms, and cardiovascular risk factors. Hypertension 45: 667‐675, 2005.
 92.Costa F, Christensen NJ, Farley G, Biaggioni I. NO modulates norepinephrine release in human skeletal muscle: Implications for neural preconditioning. Am J Physiol Regul Integr Comp Physiol 280: R1494‐R1498, 2001.
 93.Coste B, Marthur J, Schmidt M, Early T, Ranade S, Petrus M, Dubin A, Patapoutian A. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science 330: 55‐60, 2010.
 94.Crandall CG, Johnson JM, Convertino VA, Raven PB, Engelke KA. Altered thermoregulatory responses after 15 days of head‐down tilt. J Appl Physiol 77: 1863‐1867, 1994.
 95.Crandall CG, Musick J, Hatch JP, Kellogg DL, Jr., Johnson JM. Cutaneous vascular and sudomotor responses to isometric exercise in humans. J Appl Physiol 79: 1946‐1950, 1995.
 96.Crandall CG, Shibasaki M, Yen TC. Evidence that the human cutaneous venoarteriolar response is not mediated by adrenergic mechanisms. J Physiol 538: 599‐605, 2002.
 97.Crandall CG, Vongpatanasin W, Victor RG. Mechanism of cocaine‐induced hyperthermia in humans. Ann Intern Med 136: 785‐791, 2002.
 98.Cui J, Arbab‐Zadeh A, Prasad S, Durand S, Levine BD, Crandall CG. Effects of heat stress on thermoregulatory responses in congestive heart failure patients. Circulation 112: 2286‐2292, 2005.
 99.Cui J, Blaha C, Moradkhan R, Gray KS, Sinoway LI. Muscle sympathetic nerve activity responses to dynamic passive muscle stretch in humans. J Physiol 576: 625‐634, 2006.
 100.Cui J, Mascarenhas V, Moradkhan R, Blaha C, Sinoway LI. Effects of muscle metabolites on responses of muscle sympathetic nerve activity to mechanoreceptor(s) stimulation in healthy humans. Am J Physiol Regul Integr Comp Physiol 294: R458‐R466, 2008.
 101.Cui J, Sathishkumar M, Wilson TE, Shibasaki M, Davis SL, Crandall CG. Spectral characteristics of skin sympathetic nerve activity in heat‐stressed humans. Am J Physiol Heart Circ Physiol 290: H1601‐H1609, 2006.
 102.Cui J, Wilson TE, Shibasaki M, Hodges NA, Crandall CG. Baroreflex modulation of muscle sympathetic nerve activity during posthandgrip muscle ischemia in humans. J Appl Physiol (1985) 91: 1679‐1686, 2001.
 103.Dahl E, Nelson E. Electron microscopic observations on human intracranial arteries. Ii. Innervation. Arch Neurol 10: 158‐164, 1964.
 104.Dampney R, Horiuchi J, McDowall L. Hypothalamic mechanisms coordinating cardiorespiratory function during exercise and defensive behaviour. Auton Neurosci 142: 3‐10, 2008.
 105.Dampney RA. Functional organization of central pathways regulating the cardiovascular system. Physiol Rev 74: 323‐364, 1994.
 106.Dampney RA, Polson JW, Potts PD, Hirooka Y, Horiuchi J. Functional organization of brain pathways subserving the baroreceptor reflex: Studies in conscious animals using immediate early gene expression. Cell Mol Neurobiol 23: 597‐616, 2003.
 107.Daskalopoulos D, Shepherd J, Walgenbach S. Cardiopulmonary reflexes and blood pressure in exercising sinoaortic‐denervated dogs. J Appl Physiol 57: 1417‐1421, 1984.
 108.Davis SL, Shibasaki M, Low DA, Cui J, Keller DM, Purdue GF, Hunt JL, Arnoldo TB, Kowalske KJ, Crandall CG. Impaired cutaneous vasodilation and sweating in grafted skin during whole‐body heating. J Burn Care Res 28: 427‐434, 2007.
 109.Davis SL, Shibasaki M, Low DA, Cui J, Keller DM, Wingo JE, Purdue GF, Hunt JL, Arnoldo BD, Kowalske KJ, Crandall CG. Sustained impairments in cutaneous vasodilation and sweating in grafted skin following long‐term recovery. J Burn Care Res 30: 675‐685, 2009.
 110.De Angelis K, Wichi RB, Jesus WRA, Moreira ED, Morris M, Krieger EM, Irigoyen MC. Exercise training changes autonomic cardiovascular balance in mice. J Appl Physiol 96: 2174‐2178, 2004.
 111.De Burgh Daly M, Cook MN. Trigeminal and carotid body inputs controlling vascular resistance in muscle during post‐contraction hyperaemia in cats. J Physiol 515(Pt 2): 543‐554, 1999.
 112.de Mello Franco FG, Santos AC, Rondon MU, Trombetta IC, Strunz C, Braga AM, Middlekauff H, Negrao CE, Pereira Barretto AC. Effects of home‐based exercise training on neurovascular control in patients with heart failure. Eur J Heart Fail 8: 851‐855, 2006.
 113.Dean C, Coote JH. Discharge patterns in postganglionic neurones to skeletal muscle and kidney during activation of the hypothalamic and midbrain defence areas in the cat. Brain Res 377: 271‐278, 1986.
 114.Degtyarenko AM, Kaufman MP. Barosensory cells in the nucleus tractus solitarius receive convergent input from group III muscle afferents and central command. Neuroscience 140: 1041‐1050, 2006.
 115.Degtyarenko AM, Kaufman MP. Fictive locomotion and scratching inhibit dorsal horn neurons receiving thin fiber afferent input. Am J Physiol Regul Integr Comp Physiol 279: R394‐R403, 2000.
 116.Degtyarenko AM, Kaufman MP. MLR‐induced inhibition of barosensory cells in the NTS. Am J Physiol Heart Circ Physiol 289: H2584, 2005.
 117.Degtyarenko AM, Kaufman MP. Stimulation of the mesencephalic locomotor region inhibits the discharge of neurons in the superficial laminae of the dorsal horn of cats. Neurosci Lett 296: 109‐112, 2000.
 118.Degtyarenko AM, Kaufman MP. Stimulation of the MLR inhibits the discharge of dorsal horn neurons responsive to muscular contraction. Brain Res 880: 178‐182, 2000.
 119.DeLorey DS, Buckwalter JB, Mittelstadt SW, Anton MM, Kluess HA, Clifford PS. Is tonic sympathetic vasoconstriction increased in the skeletal muscle vasculature of aged canines? Am J Physiol Regul Integr Comp Physiol 299: R1342‐R1349, 2010.
 120.Delorey DS, Clifford PS, Mittelstadt S, Anton MM, Kluess HA, Tune JD, Dincer UD, Buckwalter JB. The effect of aging on adrenergic and nonadrenergic receptor expression and responsiveness in canine skeletal muscle. J Appl Physiol (1985) 112: 841‐848, 2012.
 121.DeLorey DS, Hamann JJ, Kluess HA, Clifford PS, Buckwalter JB. {alpha}‐Adrenergic receptor‐mediated restraint of skeletal muscle blood flow during prolonged exercise. J Appl Physiol 100: 1563‐1568, 2006.
 122.DeLorey DS, Wang SS, Shoemaker JK. Evidence for sympatholysis at the onset of forearm exercise. J Appl Physiol 93: 555‐560, 2002.
 123.Delp MD, O'Leary DS. Integrative control of the skeletal muscle microcirculation in the maintenance of arterial pressure during exercise. J Appl Physiol (1985) 97: 1112‐1118, 2004.
 124.Detry JM, Brengelmann GL, Rowell LB, Wyss C. Skin and muscle components of forearm blood flow in directly heated resting man. J Appl Physiol 32: 506‐511, 1972.
 125.DiCarlo SE, Bishop VS. Exercise training attenuates baroreflex regulation of nerve activity in rabbits. Am J Physiol 255: H974‐H979, 1988.
 126.DiCarlo SE, Bishop VS. Onset of exercise shifts operating point of arterial baroreflex to higher pressures. Am J Physiol 262: H303‐H307, 1992.
 127.DiCarlo SE, Chen CY, Collins HL. Onset of exercise increases lumbar sympathetic nerve activity in rats. Med Sci Sports Exerc 28: 677‐684, 1996.
 128.DiCarlo SE, Collins HL, Rodenbaugh DW, Smitha MR, Berger RD, Yeragani VK. Daily exercise reduces measures of heart rate and blood pressure variability in hypertensive rats. Clin Exp Hypertens 24: 221‐234, 2002.
 129.DiCarlo SE, Zheng H, Collins HL, Rodenbaugh DW, Patel KP. Daily exercise normalizes the number of diaphorase (NOS) positive neurons in the hypothalamus of hypertensive rats. Brain Res 955: 153‐160, 2002.
 130.Dinenno FA, Joyner MJ. Blunted sympathetic vasoconstriction in contracting skeletal muscle of healthy humans: Is nitric oxide obligatory? J Physiol 553: 281‐292, 2003.
 131.Ding Q, Vaynman S, Akhavan M, Ying Z, Gomez‐Pinilla F. Insulin‐like growth factor I interfaces with brain‐derived neurotrophic factor‐mediated synaptic plasticity to modulate aspects of exercise‐induced cognitive function. Neuroscience 140: 823‐833, 2006.
 132.Djojosugito AM, Folkow B, Kylstra PH, Lisander B, Tuttle RS. Differentiated interaction between the hypothalamic defence reaction and baroreceptor reflexes. I. Effects on heart rate and regional flow resistance. Acta Physiol Scand 78: 376‐385, 1970.
 133.Donald DE, Rowlands DJ, Ferguson DA. Similarity of blood flow in the normal and the sympathectomized dog hind limb during graded exercise. Circ Res 26: 185‐199, 1970.
 134.Dora KA. Does arterial myogenic tone determine blood flow distribution in vivo? Am J Physiol Heart Circ Physiol 289: H1323‐H1325, 2005.
 135.Drew GM, Whiting SB. Evidence for two distinct types of postsynaptic alpha‐adrenoceptor in vascular smooth muscle in vivo. Br J Pharmacol 67: 207‐215, 1979.
 136.Duprez D, Voet D, De Buyzere M, Drieghe B, Vyncke B, Mareels S, Afschrift M, Clement DL. Influence of central command and ergoreceptors on the splanchnic circulation during isometric exercise. Eur J Appl Physiol Occup Physiol 71: 459‐463, 1995.
 137.Eckberg DL, Sleight P. Human Baroreflexes in Health and Disease. Oxford: Clarendon Press, 1992, pp. 95‐119.
 138.Edholm OG, Fox RH, Macpherson RK. Vasomotor control of the cutaneous blood vessels in the human forearm. J Physiol Lond 139: 455‐465, 1957.
 139.Edvinsson L. Neurogenic mechanisms in the cerebrovascular bed. Autonomic nerves, amine receptors and their effects on cerebral blood flow. Acta Physiol Scand Suppl 427: 1‐35, 1975.
 140.Edwards MR, Martin DH, Hughson RL. Cerebral hemodynamics and resistance exercise. Med Sci Sports Exerc 34: 1207‐1211, 2002.
 141.Eiken O, Sun J, Mekjavic I. Effects of blood‐volume distribution on the characteristics of the carotid baroreflex in humans at rest and during exercise. Acta Physiol Scand 150: 89‐94, 1994.
 142.Eldridge F, Millhorn D, Kiley J, Waldrop T. Stimulation by central command of locomotion, respiration and circulation during exercise. Respir Physiol 59: 313‐337, 1985.
 143.Eldridge F, Millhorn D, Waldrop T. Exercise hyperpnea and locomotion: Parallel activation from the hypothalamus. Science 211: 844‐846, 1981.
 144.Eliasson S, Folkow B, Lindgren P, Uvnas B. Activation of sympathetic vasodilator nerves to the skeletal muscles in the cat by hypothalamic stimulation. Acta Physiol Scand 23: 333‐351, 1951.
 145.Ellsworth ML, Ellis CG, Goldman D, Stephenson AH, Dietrich HH, Sprague RS. Erythrocytes: Oxygen sensors and modulators of vascular tone. Physiology (Bethesda) 24: 107‐116, 2009.
 146.Escourrou P, Raffestin B, Papelier Y, Pussard E, Rowell LB. Cardiopulmonary and carotid baroreflex control of splanchnic and forearm circulations. Am J Physiol 264: H777‐H782, 1993.
 147.Evans C. The cerebral circulation. In: Evans C, editor. Starling's Principles of Human Physiology. London: J & A Churchill, 1941, pp. 701‐704.
 148.Evans RJ, Cunnane TC. Relative contributions of ATP and noradrenaline to the nerve evoked contraction of the rabbit jejunal artery. Naunyn Schmiedebergs Arch Pharmacol 345: 424‐430, 1992.
 149.Faber JE. Effect of local tissue cooling on microvascular smooth muscle and postjunctional alpha 2‐adrenoceptors. Am J Physiol 255: 121‐130, 1988.
 150.Faber JE. In situ analysis of alpha‐adrenoceptors on arteriolar and venular smooth muscle in rat skeletal muscle microcirculation. Circ Res 62: 37‐50, 1988.
 151.Fadel PJ, Keller DM, Watanabe H, Raven PB, Thomas GD. Noninvasive assessment of sympathetic vasoconstriction in human and rodent skeletal muscle using near‐infrared spectroscopy and Doppler ultrasound. J Appl Physiol (1985) 96: 1323‐1330, 2004.
 152.Fadel PJ, Ogoh S, Keller DM, Raven PB. Recent insights into carotid baroreflex function in humans using the variable pressure neck chamber. Exp Physiol 88: 671‐680., 2003.
 153.Fadel PJ, Ogoh S, Watenpaugh DE, Wasmund W, Olivencia‐Yurvati A, Smith ML, Raven PB. Carotid baroreflex regulation of sympathetic nerve activity during dynamic exercise in humans. Am J Physiol Heart Circ Physiol 280: H1383‐H1390., 2001.
 154.Fadel PJ, Raven PB. Human investigations into the arterial and cardiopulmonary baroreflexes during exercise. Exp Physiol 97: 39‐50, 2012.
 155.Fadel PJ, Stromstad M, Hansen J, Sander M, Horn K, Ogoh S, Smith ML, Secher NH, Raven PB. Arterial baroreflex control of sympathetic nerve activity during acute hypotension: Effect of fitness. Am J Physiol Heart Circ Physiol 280: H2524‐H2532, 2001.
 156.Fagard RH. Exercise is good for your blood pressure: Effects of endurance training and resistance training. Clin Exp Pharmacol Physiol 33: 853‐856, 2006.
 157.Fallentin N, Jensen BR, Bystrom S, Sjogaard G. Role of potassium in the reflex regulation of blood pressure during static exercise in man. J Physiol 451: 643‐651, 1992.
 158.Farmer J, Zhao X, Van Praag H, Wodtke K, Gage FH, Christie BR. Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague‐Dawley rats in vivo. Neuroscience 124: 71‐79, 2004.
 159.Fealey RD, Low PA, Thomas JE. Thermoregulatory sweating abnormalities in diabetes mellitus. Mayo Clin Proc 64: 617‐628, 1989.
 160.Fernandes IA, Mattos JD, Campos MO, Machado AC, Rocha MP, Rocha NG, Vianna LC, Nobrega AC. Selective alpha1‐adrenergic blockade disturbs the regional distribution of cerebral blood flow during static handgrip exercise. Am J Physiol Heart Circ Physiol 310: H1541‐H1548, 2016.
 161.Fisher JP, Bell MP, White MJ. Cardiovascular responses to human calf muscle stretch during varying levels of muscle metaboreflex activation. Exp Physiol 90: 773‐781, 2005.
 162.Fisher JP, Seifert T, Hartwich D, Young CN, Secher NH, Fadel PJ. Autonomic control of heart rate by metabolically sensitive skeletal muscle afferents in humans. J Physiol 588: 1117‐1127, 2010.
 163.Fisher JP, Young CN, Fadel PJ. Central sympathetic overactivity: Maladies and mechanisms. Auton Neurosci 148: 5‐15, 2009.
 164.Flavahan NA, Lindblad LE, Verbeuren TJ, Shepherd JT, Vanhoutte PM. Cooling and alpha 1‐ and alpha 2‐adrenergic responses in cutaneous veins: Role of receptor reserve. Am J Physiol 249: 950‐955, 1985.
 165.Foley CM, Mueller PJ, Hasser EM, Heesch CM. Hindlimb unloading and female gender attenuate baroreflex‐mediated sympathoexcitation. Am J Physiol Regul Integr Comp Physiol 289: R1440‐R1447, 2005.
 166.Folkow B, Haeger K, UvnÄS B. Cholinergic vasodilator nerves in the sympathetic outflow to the muscles of the hind limbs of the cat. Acta Physiologica Scandinavica 15: 401‐411, 1948.
 167.Fontana GA, Pantaleo T, Bongianni F, Cresci F, Lavorini F, Guerra CT, Panuccio P. Prostaglandin synthesis blockade by ketoprofen attenuates respiratory and cardiovascular responses to static handgrip. J Appl Physiol 78: 449‐457, 1995.
 168.Fortney SM, Mikhaylov V, Lee SM, Kobzev Y, Gonzalez RR, Greenleaf JE. Body temperature and thermoregulation during submaximal exercise after 115‐day spaceflight. Aviat Space Environ Med 69: 137‐141, 1998.
 169.Fraga R, Franco FG, Roveda F, de Matos LN, Braga AM, Rondon MU, Rotta DR, Brum PC, Barretto AC, Middlekauff HR, Negrao CE. Exercise training reduces sympathetic nerve activity in heart failure patients treated with carvedilol. Eur J Heart Fail 9: 630‐636, 2007.
 170.Friedman DB, Johnson JM, Mitchell JH, Secher NH. Neural control of the forearm cutaneous vasoconstrictor response to dynamic exercise. J Appl Physiol 71: 1892‐1896, 1991.
 171.Friedman DB, Peel C, Mitchell JH. Cardiovascular responses to voluntary and nonvoluntary static exercise in humans. J Appl Physiol 73: 1982‐1985., 1992.
 172.Galbo H, Kjaer M, Secher NH. Cardiovascular, ventilatory and catecholamine responses to maximal dynamic exercise in partially curarized man. J Physiol 389: 557‐568., 1987.
 173.Gallagher K, Fadel P, Stromstad M, Ide K, Smith S, Querry R, Raven P, Secher N. Effects of exercise pressor reflex activation on carotid baroreflex function during exercise in humans. J Physiol 533: 871‐880, 2001.
 174.Gallagher K, Fadel P, Stromstad M, Ide K, Smith S, Querry R, Raven P, Secher N. Effects of partial neuromuscular blockade on carotid baroreflex function during exercise in humans. J Physiol 533: 861‐870, 2001.
 175.Ganio MS, Schlader ZJ, Pearson J, Lucas RA, Gagnon D, Rivas E, Kowalske KJ, Crandall CG. Nongrafted skin area best predicts exercise core temperature responses in burned humans. Med Sci Sports Exerc 47: 2224‐2232, 2015.
 176.Gardiner JC, Peters CJ. Postsynaptic alpha 1‐and alpha 2‐adrenoceptor involvement in the vascular responses to neuronally released and exogenous noradrenaline in the hindlimb of the dog and cat. Eur J Pharmacol 84: 189‐198, 1982.
 177.Gava AL, Balarini CM, Peotta VA, Abreu GR, Cabral AM, Vasquez EC, Meyrelles SS. Baroreflex control of renal sympathetic nerve activity in mice with cardiac hypertrophy. Auton Neurosci 170: 62‐65, 2012.
 178.Gifford JR, Ives SJ, Park SY, Andtbacka RH, Hyngstrom JR, Mueller MT, Treiman GS, Ward C, Trinity JD, Richardson RS. α1‐ and α2‐adrenergic responsiveness in human skeletal muscle feed arteries: The role of TRPV ion channels in heat‐induced sympatholysis. Am J Physiol Heart Circ Physiol 307: H1288‐H1297, 2014.
 179.Gladwell VF, Coote JH. Heart rate at the onset of muscle contraction and during passive muscle stretch in humans: A role for mechanoreceptors. J Physiol 540: 1095‐1102, 2002.
 180.Gladwell VF, Fletcher J, Patel N, Elvidge LJ, Lloyd D, Chowdhary S, Coote JH. The influence of small fibre muscle mechanoreceptors on the cardiac vagus in humans. J Physiol 567: 713‐721, 2005.
 181.Globus M, Melamed E, Keren A, Tzivoni D, Granot C, Lavy S, Stern S. Effect of exercise on cerebral circulation. J Cereb Blood Flow Metab 3: 287‐290, 1983.
 182.Go VL, Yaksh TL. Release of substance P from the cat spinal cord. J Physiol 391: 141‐167, 1987.
 183.Gomez‐Pinilla F, Vaynman S, Ying Z. Brain‐derived neurotrophic factor functions as a metabotrophin to mediate the effects of exercise on cognition. Eur J Neurosci 28: 2278‐2287, 2008.
 184.Gonzalez‐Alonso J, Calbet JA, Nielsen B. Muscle blood flow is reduced with dehydration during prolonged exercise in humans. J Physiol 513(Pt 3): 895‐905, 1998.
 185.Goodwin GM, McCloskey DI, Mitchell JH. Cardiovascular and respiratory responses to changes in central command during isometric exercise at constant muscle tension. J Physiol 226: 173‐190, 1972.
 186.Grant RT, Holling HE. Further observations on the vascular responses of the human limb to body warming; evidence for sympathetic vasodilator nerves in the normal subject. Clin Sci Lond 3: 273‐285, 1938.
 187.Grassi G, Seravalle G, Calhoun DA, Mancia G. Physical training and baroreceptor control of sympathetic nerve activity in humans. Hypertension 23: 294‐301, 1994.
 188.Greaney J, Wenner M, Farquhar W. Exaggerated increases in blood pressure during isometric muscle contraction in hypertension: Role of purinergic receptors. Auto Neurosci 188: 51‐57, 2015.
 189.Green A, Paterson D. Identification of neurocircuitry controlling cardiovascular function in humans using functional neurosurgery: Implications for exercise control. Exp Physiol 93.9: 1022‐1028, 2008.
 190.Green A, Wang S, Purvis S, Owen S, Bain P, Stein J, Guz A, Aziz T, Paterson D. Identifying cardiorespiratory neurocircuitry involved in central command during exercise in humans. J Physiol 578: 605‐612, 2007.
 191.Green DJ, Maiorana AJ, Siong JH, Burke V, Erickson M, Minson CT, Bilsborough W, O'Driscoll G. Impaired skin blood flow response to environmental heating in chronic heart failure. Eur Heart J 27: 338‐343, 2006.
 192.Greenberg SS, Diecke FP, Peevy K, Tanaka TP. Release of norepinep‐hrine from adrenergic nerve endings of blood vessels is modulated by endothelium‐derived relaxing factor. Am J Hypertens 3: 211‐218, 1990.
 193.Greenwood BN, Kennedy S, Smith TP, Campeau S, Day HEW, Fleshner M. Voluntary freewheel running selectively modulates catecholamine content in peripheral tissue and c‐fos expression in the central sympathetic circuit following exposure to uncontrollable stress in rats. Neuroscience 120: 269‐281, 2003.
 194.Guild SJ, Barrett CJ, Malpas SC. Long‐term recording of sympathetic nerve activity: The new frontier in understanding the development of hypertension? Clin Exp Pharmacol Physiol 32: 433‐439, 2005.
 195.Gullestad L, Hallen J, Sejersted OM. Variable effects of beta‐adrenoceptor blockade on muscle blood flow during exercise. Acta Physiol Scand 149: 257‐271, 1993.
 196.Guo A, Vulchanova L, Wang J, Li X, Elde R. Immunocytochemical localization of the vanilloid receptor 1 (VR1): relationship to neuropeptides, the P2X3 purinoceptor and IB4 binding sites. Eur J Neurosci 11: 946‐958, 1999.
 197.Guyenet PG. The sympathetic control of blood pressure. Nat Rev Neurosci 7: 335‐346, 2006.
 198.Haidet GC, Parsons D. Reduced exercise capacity in senescent beagles: An evaluation of the periphery. Am J Physiol 260: H173‐H182, 1991.
 199.Hainsworth R. Reflexes from the heart. Physiol Rev 71: 617‐658, 1991.
 200.Hajduczok G, Hade JS, Mark AL, Williams JL, Felder RB. Central command increases sympathetic nerve activity during spontaneous locomotion in cats. Circ Res 69: 66‐75, 1991.
 201.Hamann JJ, Buckwalter JB, Clifford PS. Vasodilatation is obligatory for contraction‐induced hyperaemia in canine skeletal muscle. J Physiol 557: 1013‐1020, 2004.
 202.Hamann JJ, Buckwalter JB, Valic Z, Clifford PS. Sympathetic restraint of muscle blood flow at the onset of dynamic exercise. J Appl Physiol 92: 2452‐2456, 2002.
 203.Hamann JJ, Valic Z, Buckwalter JB, Clifford PS. Muscle pump does not enhance blood flow in exercising skeletal muscle. J Appl Physiol 94: 6‐10, 2003.
 204.Hamed AT, Jandhyala BS, Lokhandwala MF. Evaluation of the role of alpha‐1 and alpha‐2 adrenoceptors in the maintenance of neurogenic tone to the hindlimb vasculature. J Pharmacol Exp Ther 238: 599‐605, 1986.
 205.Hamilton MT, Hamilton DG, Zderic TW. Role of low energy expenditure and sitting in obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease. Diabetes 56: 2655‐2667, 2007.
 206.Hamilton MT, Hamilton DR, Zderic TW. Exercise physiology versus inactivity physiology: An essential concept for understanding lipoprotein lipase regulation. Exerc Sport Sci Rev 32: 161‐166, 2004.
 207.Hand GA, Kramer GL, Petty F, Ordway GA, Wilson LB. Excitatory amino acid concentrations in the spinal dorsal horn of cats during muscle contraction. J Appl Physiol 81: 368‐373, 1996.
 208.Hanna RL, Hayes SG, Kaufman MP. Alpha, beta‐methylene ATP elicits a reflex pressor response arising from muscle in decerebrate cats. J Appl Physiol 93: 834‐841, 2002.
 209.Hansen J, Thomas GD, Harris SA, Parsons WJ, Victor RG. Differential sympathetic neural control of oxygenation in resting and exercising human skeletal muscle. J Clin Invest 98: 584‐596, 1996.
 210.Hansen J, Thomas GD, Jacobsen TN, Victor RG. Muscle metaboreflex triggers parallel sympathetic activation in exercising and resting human skeletal muscle. Am J Physiol 266: H2508‐H2514, 1994.
 211.Hartling OJ, Noer I, Svendsen TL, Clausen JP, Trap‐Jensen J. Selective and non‐selective beta‐adrenoreceptor blockade in the human forearm. Clin Sci (Lond) 58: 279‐286, 1980.
 212.Hartling OJ, Trap‐Jensen J. Haemodynamic and metabolic effects of alpha‐adrenoceptor blockade with phentolamine at rest and during forearm exercise. Clin Sci (Lond) 65: 247‐253, 1983.
 213.Hasking GJ, Esler MD, Jennings GL, Dewar E, Lambert G. Norepinephrine spillover to plasma during steady‐state supine bicycle exercise. Comparison of patients with congestive heart failure and normal subjects. Circulation 78: 516‐521, 1988.
 214.Hasser EM, Moffitt JA. Regulation of sympathetic nervous system function after cardiovascular deconditioning. Ann NY Acad Sci 940: 454‐468, 2001.
 215.Hayes SG, Kaufman MP. Gadolinium attenuates exercise pressor reflex in cats. Am J Physiol Heart Circ Physiol 280: H2153‐H2161, 2001.
 216.Hayes SG, Kindig AE, Kaufman MP. Comparison between the effect of static contraction and tendon stretch on the discharge of group III and IV muscle afferents. J Appl Physiol (1985) 99: 1891‐1896, 2005.
 217.Hegarty AA, Felder RB. Antagonism of vasopressin V1 receptors in NTS attenuates baroreflex control of renal nerve activity. Am J Physiol 269 (Heart Circ Physiol 38): H1080‐H1086, 1995.
 218.Hellsten Y, Nyberg M, Mortensen SP. Contribution of intravascular versus interstitial purines and nitric oxide in the regulation of exercise hyperaemia in humans. J Physiol 590: 5015‐5023, 2012.
 219.Hellstrom G, Fischer‐Colbrie W, Wahlgren NG, Jogestrand T. Carotid artery blood flow and middle cerebral artery blood flow velocity during physical exercise. J Appl Physiol 81: 413‐418, 1996.
 220.Heymans C, Neil E. Reflexogenic areas in the cardiovascular system. British Journal of Surgery 46(195): 92, 1958.
 221.Hill JM, Adreani CM, Kaufman MP. Muscle reflex stimulates sympathetic postganglionic efferents innervating triceps surae muscles of cats. Am J Physiol 271: H38‐H43, 1996.
 222.Hill JM, Kaufman MP. Attenuating effects of intrathecal clonidine on the exercise pressor reflex. J Appl Physiol 70: 516‐522, 1991.
 223.Hilton S, Marshall J, Timms R. Ventral medullary relay neurons in the pathway from the defence areas of the cat and their effect on blood pressure. J Physiol 345: 149‐166, 1983.
 224.Hirst GD, Jobling P. The distribution of gamma‐adrenoceptors and P2 purinoceptors in mesenteric arteries and veins of the guinea‐pig. Br J Pharmacol 96: 993‐999, 1989.
 225.Hník P, Holas M, Krekule I, Kříž N, Mejsnar J, Smieško V, Ujec E, Vyskočil F. Work‐induced potassium changes in skeletal muscle and effluent venous blood assessed by liquid ion‐exchanger microelectrodes. Pflügers Archiv 362: 85‐94, 1976.
 226.Ho CW, Beard JL, Farrell PA, Minson CT, Kenney WL. Age, fitness, and regional blood flow during exercise in the heat. J Appl Physiol 82: 1126‐1135, 1997.
 227.Hökfelt T, Elde R, Johansson O, Luft R, Nilsson G, Arimura A. Immunohistochemical evidence for separate populations of somatostatin‐containing and substance P‐containing primary afferent neurons in the rat. Neuroscience 1: 131‐136, 1976.
 228.Holowatz LA, Kenney WL. Peripheral mechanisms of thermoregulatory control of skin blood flow in aged humans. J Appl Physiol 109: 1538‐1544, 2010.
 229.Holowatz LA, Thompson‐Torgerson CS, Kenney WL. Altered mechanisms of vasodilation in aged human skin. Exerc Sport Sci Rev 35: 119‐125, 2007.
 230.Horn PT, Kohli JD, Listinsky JJ, Goldberg LI. Regional variation in the alpha‐adrenergic receptors in the canine resistance vessels. Naunyn Schmiedebergs Arch Pharmacol 318: 166‐172, 1982.
 231.Huang SY, Sun S, Droma T, Zhuang J, Tao JX, McCullough RG, McCullough RE, Micco AJ, Reeves JT, Moore LG. Internal carotid arterial flow velocity during exercise in Tibetan and Han residents of Lhasa (3,658 m). J Appl Physiol 73: 2638‐2642, 1992.
 232.Huang SY, Tawney KW, Bender PR, Groves BM, McCullough RE, McCullough RG, Micco AJ, Manco‐Johnson M, Cymerman A, Greene ER, et al. Internal carotid flow velocity with exercise before and after acclimatization to 4,300 m. J Appl Physiol 71: 1469‐1476, 1991.
 233.Huber DA, Schreihofer AM. Altered regulation of the rostral ventrolateral medulla in hypertensive obese Zucker rats. Am J Physiol Heart Circ Physiol 301: H230‐H240, 2011.
 234.Ichinose M, Saito M, Fujii N, Ogawa T, Hayashi K, Kondo N, Nishiyasu T. Modulation of the control of muscle sympathetic nerve activity during incremental leg cycling. J Physiol 586: 2753‐2766, 2008.
 235.Ichinose M, Saito M, Kondo N, Nishiyasu T. Time‐dependent modulation of arterial baroreflex control of muscle sympathetic nerve activity during isometric exercise in humans. Am J Physiol Heart Circ Physiol 290: H1419‐H1426, 2006.
 236.Ichiyama RM, Gilbert AB, Waldrop TG, Iwamoto GA. Changes in the exercise activation of diencephalic and brainstem cardiorespiratory areas after training. Brain Res 947: 225‐233, 2002.
 237.Ide K, Boushel R, Sorensen HM, Fernandes A, Cai Y, Pott F, Secher NH. Middle cerebral artery blood velocity during exercise with beta‐1 adrenergic and unilateral stellate ganglion blockade in humans. Acta Physiol Scand 170: 33‐38, 2000.
 238.Ide K, Eliasziw M, Poulin MJ. The relationship between middle cerebral artery blood velocity and end‐tidal PCO2 in the hypocapnic‐hypercapnic range in humans. J Appl Physiol 95: 129‐137, 2003.
 239.Ide K, Secher NH. Cerebral blood flow and metabolism during exercise. Prog Neurobiol 61: 397‐414, 2000.
 240.Iellamo F, Legramante JM, Raimondi G, Peruzzi G. Baroreflex control of sinus node during dynamic exercise in humans: Effects of central command and muscle reflexes. Am J Physiol 272: H1157‐H1164, 1997.
 241.Ishide T, Mancini M, Maher TJ, Chayaikul P, Ally A. Rostral ventrolateral medulla opioid receptor activation modulates glutamate release and attenuates the exercise pressor reflex. Brain Res 865: 177‐185, 2000.
 242.Ishide T, Nauli SM, Maher TJ, Ally A. Cardiovascular responses and neurotransmitter changes following blockade of nNOS within the ventrolateral medulla during static muscle contraction. Brain Res 977: 80‐89, 2003.
 243.Ives S, Amann M, Venturelli M, Witman M, Groot H, Wray D, Morgan D, Stehlik J, Richardson R. The mechanoreflex and hemodynamic responses to passive leg movement in heart failure. Med Sci Sports Exerc 48: 368‐376, 2016.
 244.Ives S, McDaniel J, Witman M, Richardson R. Passive limb movement: Evidence of mechanoreflex sex specificity. Am J Physiol 304: H154‐H161, 2013.
 245.Ives SJ, Andtbacka RH, Kwon SH, Shiu YT, Ruan T, Noyes RD, Zhang QJ, Symons JD, Richardson RS. Heat and α1‐adrenergic responsiveness in human skeletal muscle feed arteries: The role of nitric oxide. J Appl Physiol (1985) 113: 1690‐1698, 2012.
 246.Ives SJ, Andtbacka RH, Noyes RD, McDaniel J, Amann M, Witman MA, Symons JD, Wray DW, Richardson RS. Human skeletal muscle feed arteries studied in vitro: The effect of temperature on α(1)‐adrenergic responsiveness. Exp Physiol 96: 907‐918, 2011.
 247.Iwamoto GA, Kaufman MP. Caudal ventrolateral medullary cells responsive to static muscular contraction. J Appl Physiol 62: 149‐157, 1987.
 248.Iwamoto GA, Kaufman MP, Botterman BR, Mitchell JH. Effects of lateral reticular nucleus lesions on the exercise pressor reflex in cats. Circ Res 51: 400‐403, 1982.
 249.Iwamoto GA, Nelson AJ. Commentary on Viewpoint: Exercise and cardiovascular risk reduction: Time to update the rationale for exercise? J Appl Physiol 105: 773, 2008.
 250.Jankowski MP, Rau KK, Ekmann KM, Anderson CE, Koerber HR. Comprehensive phenotyping of group III and IV muscle afferents in mice. J Neurophysiol 109: 2374‐2381, 2013.
 251.Johansson JE. Ueber die Einwirkung der Muskelthatigkeit auf die Athmung und die Hertzhiitigkeit. Skandinaviesches Archiv fiir Physiologie 5: 20‐66, 1895.
 252.Johnson CD, Coney AM, Marshall JM. Roles of norepinephrine and ATP in sympathetically evoked vasoconstriction in rat tail and hindlimb in vivo. Am J Physiol Heart Circ Physiol 281: H2432‐H2440, 2001.
 253.Johnson JM. Exercise and the cutaneous circulation. Exer Sports Sci Rev 20: 59‐97, 1992.
 254.Johnson JM, Minson CT, Kellogg DL. Cutaneous vasodilator and vasoconstrictor mechanisms in temperature regulation. Compr Physiol 4: 33‐89, 2014.
 255.Johnson JM, Park MK. Effect of heat stress on cutaneous vascular responses to the initiation of exercise. J Appl Physiol 53: 744‐749, 1982.
 256.Johnson JM, Pergola PE, Liao FK, Kellogg DL, Jr., Crandall CG. Skin of the dorsal aspect of human hands and fingers possesses an active vasodilator system. J Appl Physiol 78: 948‐954, 1995.
 257.Johnson JM, Proppe DW. Cardiovascular adjustments to heat stress. In: Blatteis C, Fregly M, editors. Handbook of Physiology: Adaptations to the Environment. Bethesda, MD: American Physiological Society, 1996, pp. 215‐243.
 258.Jorgensen LG, Perko G, Secher NH. Regional cerebral artery mean flow velocity and blood flow during dynamic exercise in humans. J Appl Physiol 73: 1825‐1830, 1992.
 259.Jorgensen LG, Perko M, Hanel B, Schroeder TV, Secher NH. Middle cerebral artery flow velocity and blood flow during exercise and muscle ischemia in humans. J Appl Physiol 72: 1123‐1132, 1992.
 260.Joyner MJ. Baroreceptor function during exercise: Resetting the record. Exp Physiol 91: 27‐36, 2006.
 261.Joyner MJ, Green DJ. Exercise protects the cardiovascular system: Effects beyond traditional risk factors. J Physiol 587: 5551‐5558, 2009.
 262.Joyner MJ, Nauss LA, Warner MA, Warner DO. Sympathetic modulation of blood flow and O2 uptake in rhythmically contracting human forearm muscles. Am J Physiol 263: 1078‐1083, 1992.
 263.Juhlin‐Dannfelt A, Astrom H. Influence of ß‐adrenoceptor blockade on leg blood flow and lactate release in man. Scand J Clin Lab Invest 39: 179‐183, 1979.
 264.Kamiya A, Michikami D, Fu Q, Niimi Y, Iwase S, Mano T, Suzumura A. Static handgrip exercise modifies arterial baroreflex control of vascular sympathetic outflow in humans. Am J Physiol Regul Integr Comp Physiol 281: R1134‐R1139, 2001.
 265.Kanbar R, Orea V, Barres C, Julien C. Baroreflex control of renal sympathetic nerve activity during air‐jet stress in rats. Am J Physiol Regul Integr Comp Physiol 292: R362‐R367, 2007.
 266.Kaufman MP. The exercise pressor reflex in animals. Exp Physiol 97: 51‐58, 2012.
 267.Kaufman MP, Forster HV. Reflexes controlling circulatory, ventilatory and airway responses to exercise. In: Section 12, Exercise: Regulation and Integration of Multiple Systems. Bethsda, MD: American Physiological Society, 1996, pp. 381‐447.
 268.Kaufman MP, Hayes SG. The exercise pressor reflex. Clin Auton Res 12: 429‐439, 2002.
 269.Kaufman MP, Iwamoto GA, Longhurst JC, Mitchell JH. Effects of capsaicin and bradykinin on afferent fibers with ending in skeletal muscle. Circ Res 50: 133‐139, 1982.
 270.Kaufman MP, Kozlowski GP, Rybicki KJ. Attenuation of the reflex pressor response to muscular contraction by a substance P antagonist. Brain Res 333: 182‐184, 1985.
 271.Kaufman MP, Longhurst JC, Rybicki KJ, Wallach JH, Mitchell JH. Effects of static muscle contraction on impulse activity of groups III and IV afferents in cats. J Appl Physiol 55: 105‐112, 1983.
 272.Kaufman MP, Rybicki KJ, Kozlowski GP, Iwamoto GA. Immunoneutralization of substance P attenuates the reflex pressor response to muscular contraction. Brain Res 377: 199‐203, 1986.
 273.Kaufman MP, Waldrop TG, Rybicki KJ, Ordway GA, Mitchell JH. Effects of static and rhythmic twitch contractions on the discharge of group III and IV muscle afferernts. Cardiovasc Res 18: 663‐668, 1984.
 274.Kawabe T, Kawabe K, Sapru HN. Cardiovascular responses to somatosensory stimulation and their modulation by baroreflex mechanisms. Clin Exp Hypertens 29: 403‐418, 2007.
 275.Keller DM, Fadel PJ, Ogoh S, Brothers RM, Hawkins M, Olivencia‐Yurvati A, Raven PB. Carotid baroreflex control of leg vasculature in exercising and non‐exercising skeletal muscle in humans. J Physiol 561: 283‐293, 2004.
 276.Keller DM, Ogoh S, Greene S, Olivencia‐Yurvati A, Raven PB. Inhibition of KATP channel activity augments baroreflex‐mediated vasoconstriction in exercising human skeletal muscle. J Physiol 561: 273‐282, 2004.
 277.Kellogg DL, Jr. In vivo mechanisms of cutaneous vasodilation and vasoconstriction in humans during thermoregulatory challenges. J Appl Physiol 100: 1709‐1718, 2006.
 278.Kellogg DL, Jr., Johnson JM, Kenney WL, Pérgola PE, Kosiba WA. Mechanisms of control of skin blood flow during prolonged exercise in humans. Am J Physiol 265: H562‐H568, 1993.
 279.Kellogg DL, Jr., Johnson JM, Kosiba WA. Competition between cutaneous active vasoconstriction and active vasodilation during exercise in man. Am J Physiol 261: H1184‐H1189, 1991.
 280.Kellogg DL, Jr., Johnson JM, Kosiba WA. Control of internal temperature threshold for active cutaneous vasodilation by dynamic exercise. J Appl Physiol 71: 2476‐2482, 1991.
 281.Kellogg DL, Jr., Johnson JM, Kosiba WA. Selective abolition of adrenergic vasoconstrictor responses in skin by local iontophoresis of bretylium. Am J Physiol Heart Circ Physiol 257: H1599‐H1606, 1989.
 282.Kellogg DL, Jr., Pérgola PE, Piest KL, Kosiba WA, Crandall CG, Johnson JM. Cutaneous active vasodilation in humans is mediated by cholinergic nerve co‐transmission. Circ Res 77: 1222‐1228, 1995.
 283.Kennedy C, Saville VL, Burnstock G. The contributions of noradrenaline and ATP to the responses of the rabbit central ear artery to sympathetic nerve stimulation depend on the parameters of stimulation. Eur J Pharmacol 122: 291‐300, 1986.
 284.Kenney WL. Thermoregulation at rest and during exercise in healthy older adults. Exerc Sport Sci Rev 25: 41‐76, 1997.
 285.Kenney WL, Craighead DH, Alexander LM. Heat waves, aging and human cardiovascular health. Med Sci Sports Exerc 46: 1891‐1899, 2014.
 286.Kenney WL, Munce TA. Invited review: Aging and human temperature regulation. J Appl Physiol 95: 2598‐2603, 2003.
 287.Kenney WL, Tankersley CG, Newswanger DL, Puhl SM. α1‐Adrenergic blockade does not alter control of skin blood flow during exercise. Amer J Physiol 260: H855‐H861, 1991.
 288.Kenney WL, Zappe DH, Tankersley CG, Derr JA. Effect of systemic yohimbine on the control of skin blood flow during local heating and dynamic exercise. Am J Physiol 266: H371‐H376, 1994.
 289.Kenny GP, Sigal RJ, McGinn R. Body temperature regulation in diabetes. Temperature (Austin) 3: 119‐145, 2016.
 290.Kenny GP, Yardley J, Brown C, Sigal RJ, Jay O. Heat stress in older individuals and patients with common chronic diseases. Cmaj 182: 1053‐1060, 2010.
 291.Kiely J, Gordon F. Role of rostral ventrolateral medulla in centrally mediated pressor responses. Am J Physiol 267: H1549‐H1556, 1994.
 292.Kiely JM, Gordon FJ. Non‐NMDA receptors in the rostral ventrolateral medulla mediate somatosympathetic pressor responses. J Auton Nerv Syst 43: 231‐239, 1993.
 293.Kindig AE, Heller TB, Kaufman MP. VR‐1 receptor blockade attenuates the pressor response to capsaicin but has no effect on the pressor response to contraction in cats. Am J Physiol Heart Circ Physiol 288: H1867‐H1873, 2005.
 294.Kirby BS, Voyles WF, Carlson RE, Dinenno FA. Graded sympatholytic effect of exogenous ATP on postjunctional alpha‐adrenergic vasoconstriction in the human forearm: implications for vascular control in contracting muscle. J Physiol 586: 4305‐4316, 2008.
 295.Klabunde RE. Attenuation of reactive and active hyperemia by sympathetic stimulation in dog gracilis muscle. Am J Physiol Heart Circ Physiol 251: H1183‐H1187, 1986.
 296.Kleiber AC, Zheng H, Schultz HD, Peuler JD, Patel KP. Exercise training normalizes enhanced glutamate‐mediated sympathetic activation from the PVN in heart failure. Am J Physiol Regul Integr Comp Physiol 294: R1863‐R1872, 2008.
 297.Kluess HA, Buckwalter JB, Hamann JJ, Clifford PS. Elevated temperature decreases sensitivity of P2X purinergic receptors in skeletal muscle arteries. J Appl Physiol 99: 995‐998, 2005.
 298.Kluess HL, Buckwalter JB, Hamann JJ, DeLorey DS, Clifford PS. Frequency and pattern dependence of adrenergic and purinergic vasoconstriction in skeletal muscle arteries. Exper Physiol 91: 1051‐1058, 2006.
 299.Knochel JP. Heat stroke and related heat stress disorders. Dis Mon 35: 301‐377, 1989.
 300.Koba S, Xing J, Sinoway LI, Li J. Differential sympathetic outflow elicited by active muscle in rats. Am J Physiol Heart Circ Physiol 293: H2335‐H2343, 2007.
 301.Koba S, Yoshida T, Hayashi N. Differential sympathetic outflow and vasoconstriction responses at kidney and skeletal muscles during fictive locomotion. Am J Physiol Heart Circ Physiol 290: H861‐H868, 2006.
 302.Koba S, Yoshida T, Hayashi N. Sympathetically induced renal vasoconstriction during stimulation of mesencephalic locomotor region in rats. Auton Neurosci 121: 40‐46, 2005.
 303.Koike HA, Mark AL, Heistad DD, Schmid PG. Influence of cardiopulmonary vagal afferent activity on carotid chemoreceptor and baroreceptor reflexes in the dog. Circ Res 37: 422‐429, 1975.
 304.Kowalchuk J, Klein C, Hughson R. The effect of beta‐adrenergic blockade on leg blood flow with repeated maximal contractions of the triceps surae muscle group in man. Eur J Appl Physiol Occup Physiol 60: 360‐364, 1990.
 305.Kozelka JW, Christy GW, Wurster RD. Ascending pathways mediating somatoautonomic reflexes in exercising dogs. J Appl Physiol (1985) 62: 1186‐1191, 1987.
 306.Kozelka JW, Christy GW, Wurster RD. Somato‐autonomic reflexes in anesthetized and unanesthetized dogs. J Auton Nerv Syst 5: 63‐70, 1982.
 307.Kramer AF, Erickson KI. Capitalizing on cortical plasticity: influence of physical activity on cognition and brain function. Trends Cogn Sci 11: 342‐348, 2007.
 308.Kramer JM, Beatty JA, Little HR, Plowey ED, Waldrop TG. Chronic exercise alters caudal hypothalamic regulation of the cardiovascular system in hypertensive rats. Am J Physiol Regul Integr Comp Physiol 280: R389‐R397, 2001.
 309.Kramer JM, Beatty JA, Plowey ED, Waldrop TG. Exercise and hypertension: A model for central neural plasiticity. Clin Exp Pharmacol Physiol 29: 122‐126, 2002.
 310.Kregel KC, Allen DL, Booth FW, Fleshner MR, Henriksen EJ, Musch TI, O'Leary DS, Parks CM, Poole DC, Ra'anan AW, Sheriff DD, Sturek MS, Toth LA. Resource Book for the Design of Animal Exercise Protocols. Bethesda, MD: American Physiological Society, 2006.
 311.Krieger EM, Da Silva GJJ, Negrao CE. Effects of exercise training on baroreflex control of the cardiovascular system. Ann N Y Acad Sci 940: 338‐347, 2001.
 312.Krogh A, Lindhard J. The regulation of respiration and circulation dur‐ing the initial stages of muscular work. J Physiol 47: 112‐136, 1913.
 313.Kubo T, Kihara M. Modulation of the aortic baroreceptor reflex by neuropeptide Y, neurotensin and vasopressin microinjected into the nucleus tractus solitarii of the rat. Naunyn Schmiedebergs Arch Pharmacol 342: 182‐188, 1990.
 314.Kurjiaka DT, Segal SS. Interaction between conducted vasodilation and sympathetic nerve activation in arterioles of hamster striated muscle. Circ Res 76: 885‐891, 1995.
 315.Lai Y, Thomas GD, Yue Y, Yang HT, Li D, Long C, Judge L, Bostick B, Chamberlain JS, Terjung RL, Duan D. Dystrophins carrying spectrin‐like repeats 16 and 17 anchor nNOS to the sarcolemma and enhance exercise performance in a mouse model of muscular dystrophy. J Clin Invest 119: 624‐635, 2009.
 316.Lassen NA. Cerebral blood flow and oxygen consumption in man. Physiol Rev 39: 183‐238, 1959.
 317.Laughlin MH. Skeletal muscle blood flow capacity: Role of muscle pump in exercise hyperemia. Am J Physiol 253: H993‐H1004, 1987.
 318.Laughlin MH, Armstrong RB. Adrenoreceptor effects on rat muscle blood flow during treadmill exercise. J Appl Physiol 62: 1465‐1472, 1987.
 319.Laughlin MH, Armstrong RB. Rat muscle blood flows as a function of time during prolonged slow treadmill exercise. Am J Physiol 244: H814‐H824, 1983.
 320.Laughlin MH, Davis MJ, Secher NH, van Lieshout JJ, Arce‐Esquivel AA, Simmons GH, Bender SB, Padilla J, Bache RJ, Merkus D, Duncker DJ. Peripheral circulation. Compr Physiol 2: 321‐447, 2012.
 321.Lautt WW. Hepatic nerves: A review of their functions and effects. Can J Physiol Pharmacol 58: 105‐123, 1980.
 322.Lautt WW. Resistance or conductance for expression of arterial vascular tone. Microvasc Res 37: 230‐236, 1989.
 323.Lautt WW, Lockhart LK, Legare DJ. Adenosine modulation of vasoconstrictor responses to stimulation of sympathetic nerves and norepinephrine infusion in the superior mesenteric artery of the cat. Can J Phyiol Pharmacol 66: 937‐941, 1988.
 324.Laye MJ, Thyfault JP, Stump CS, Booth FW. Inactivity induces increases in abdominal fat. J Appl Physiol 102: 1341‐1347, 2007.
 325.Leal AK, McCord JL, Tsuchimochi H, Kaufman MP. Blockade of the TP receptor attenuates teh exercise pressor reflex in decerebrated rats with chronic femoral artery occlusion. Am J Physiol 301: H2140‐H2146, 2011.
 326.Leal AK, Mitchell JH, Smith SA. Treatment of muscle mechanoreflex dysfunction in hypertension: Effects of l‐arginine dialysis in the nucleus tractus solitarii. Exp Physiol 98: 1337‐1348, 2013.
 327.Leal AK, Yamauchi K, Kim J, Ruiz‐Velasco V, Kaufman MP. Peripheral delta‐opioid receptors attenuate the exercise pressor reflex. Am J Physiol 305: H1246‐H1255, 2013.
 328.Lee F, Shoemaker JK, McQuillan PM, Kunselman AR, Smith MB, Yang QX, Smith H, Gray K, Sinoway LI. Effects of forearm bier block with bretylium on the hemodynamic and metabolic responses to handgrip. Am J Physiol Heart Circ Physiol 279: H586‐H593, 2000.
 329.Lee SM, Williams WJ, Schneider SM. Role of skin blood flow and sweating rate in exercise thermoregulation after bed rest. J Appl Physiol 92: 2026‐2034, 2002.
 330.Leonard B, Mitchell JH, Mizuno M, Rube N, Saltin B, Secher NH. Partial neuromuscular blockade and cardiovascular responses to static exercise in man. J Physiol 359: 365‐379., 1985.
 331.Lewis C, Neidhart S, Holy C, North RA, Buell G, Surprenant A. Coexpression of P2X2 and P2X3 receptor subunits can account for ATP‐gated currents in sensory neurons. Nature 377: 432‐435, 1995.
 332.Lewis T, Pickering GW. Vasodilation in the limbs in response to warming the body; with evidence for sympathetic vasodilator nerves in man. Heart 16: 33‐51, 1931.
 333.Leyk D, Essfeld D, Baum K, Stegemann J. Early leg blood flow adjustment during dynamic foot plantarflexions in upright and supine body position. Int J Sports Med 15: 447‐452, 1994.
 334.Li J, Gao Z, Kehoe V, Xing J, King N, Sinoway L. Interstitial adenosine triphosphate modulates muscle afferent nerve‐mediated pressor reflex. Musc Nerve 38: 972‐977, 2008.
 335.Li J, Hand GA, Potts JT, Wilson LB, Mitchell JH. c‐Fos expression in the medulla induced by static muscle contraction in cats. Am J Physiol 272: H48‐H56, 1997.
 336.Li J, King NC, Sinoway LI. ATP concentrations and muscle tension increase linearly with muscle contraction. J Appl Physiol 95: 577‐583, 2003.
 337.Li J, Maile MD, Sinoway AN, Sinoway LI. Muscle pressor reflex: Potential role of vanilloid type 1 receptor and acid‐sensing ion channel. J Appl Physiol 97: 1709‐1714, 2004.
 338.Li J, Mitchell JH. c‐Fos expression in the midbrain periaqueductal gray during static muscle contraction. Am J Physiol 279: H2986‐H2993, 2000.
 339.Li J, Mitchell JH. Role of NO in modulating neuronal activity in superficial dorsal horn of spinal cord during exercise pressor reflex. Am J Physiol 283: H1012‐H1018, 2002.
 340.Li J, Potts JT, Kramer GL, Petty F, Mitchell JH. Activation of skeletal muscle afferents evokes release of glutamate in the subretrofacial nucleus (SRF) of cats. Brain Res 894: 249‐254, 2001.
 341.Li J, Sinoway LI. ATP stimulates chemically sensitive and sensitizes mechanically sensitive afferents. Am J Physiol 283: H2636‐H2643, 2002.
 342.Liang N, Mitchell JH, Smith SA, Mizuno M. Exaggerated sympathetic and cardiovascular responses to stimulation of the mesencephalic locomotor region in spontaneously hypertensive rats. Am J Physiol 310: H123‐H131, 2016.
 343.Light AR, Hughen RW, Zhang J, Rainier J, Liu Z, Lee J. Dorsal root ganglion neurons innervating skeletal muscle respond to physiological combinations of protons, ATP, and lactate mediated ASIC, P2X, and TRPV1. J Neurophysiol 100: 1184‐1201, 2008.
 344.Lillaney R, Maher TJ, Chaiyakul P, Ally A. Changes in extracellular glutamate and pressor response during muscle contraction following AMPA‐receptor blockade in the RVLM and CVLM. Brain Res 844: 164‐173, 1999.
 345.Linkis P, Jorgensen LG, Olesen HL, Madsen PL, Lassen NA, Secher NH. Dynamic exercise enhances regional cerebral artery mean flow velocity. J Appl Physiol 78: 12‐16, 1995.
 346.Little HR, Kramer JM, Beatty JA, Waldrop TG. Chronic exercise increases GAD gene expression in the caudal hypothalamus of spontaneously hypertensive rats. Mol Brain Res 95: 48‐54, 2001.
 347.Longhurst JC, Musch TI, Ordway GA. O2 consumption during exercise in dogs–‐roles of splenic contraction and alpha‐adrenergic vasoconstriction. Am J Physiol 251: 502‐509, 1986.
 348.Lorenz RR, Vanhoutte PM. Inhibition of adrenergic neurotransmission in isolated veins of the dog by potassium ions. J Physiol 246: 479‐500, 1975.
 349.Lucas SJ, Tzeng YC, Galvin SD, Thomas KN, Ogoh S, Ainslie PN. Influence of changes in blood pressure on cerebral perfusion and oxygenation. Hypertension 55: 698‐705, 2010.
 350.Lundberg JM, Modin A. Inhibition of sympathetic vasoconstriction in pigs in vivo by the neuropeptide Y‐Y1 receptor antagonist BIBP 3226. Br J Pharmacol 116: 2971‐2982, 1995.
 351.Lynn RB, Sancetta SM, Simeone FA, Scott RW. Observations on the circulation in high spinal anesthesia. Surgery 32: 195‐213, 1952.
 352.Macarthur H, Mattammal MB, Westfall TC. A new perspective on the inhibitory role of nitric oxide in sympathetic neurotransmission. Biochem Biophys Res Commun 216: 686‐692, 1995.
 353.Macefield VG, Henderson LA. Real‐time imaging of the medullary circuitry involved in the generation of spontaneous muscle sympathetic nerve activity in awake subjects. Hum Brain Mapp 31: 539‐549, 2010.
 354.Mack G, Nose H, Nadel ER. Role of cardiopulmonary baroreflexes during dynamic exercise. J Appl Physiol 65: 1827‐1832., 1988.
 355.Mack GW, Cordero D, Peters J. Baroreceptor modulation of active cutaneous vasodilation during dynamic exercise in humans. J Appl Physiol 90: 1464‐1473, 2001.
 356.Mack GW, Nishiyasu T, Shi X. Baroreceptor modulation of cutaneous vasodilator and sudomotor responses to thermal stress in humans. J Physiol (Lond) 483: 537‐547, 1995.
 357.Malpas SC. Sympathetic nervous system overactivity and its role in the development of cardiovascular disease. Physiol Rev 90: 513‐557, 2010.
 358.Mancia G, Iannos J, Jamieson GG, Lawrence RH, Sharman PR, Ludbrook J. Effect of isometric hand‐grip exercise on the carotid sinus baroreceptor reflex in man. Clin Sci Mol Med 54: 33‐37., 1978.
 359.Mancia G, Mark AL. Arterial baroreflexes in humans. In: Handbook of Physiology the Cardiovascular System Peripheral Circulation and Organ Blood Flow. Bethesda, MD: American Physiological Society, 1983, pp. 755‐793.
 360.Marey EJ. Physiologie médicale de la circulation du sang. Paris: Delahaye, 1863, pp. 1‐568.
 361.Mark AL, Mancia G. Cardiopulmonary baroreflexes in humans. In: Handbook of Physiology the Cardiovascular System Peripheral Circulation and Organ Blood Flow. Bethesda, MD: American Physiological Society, 1983, pp. 795‐813.
 362.Mark AL, Victor RG, Nerhed C, Wallin BG. Microneurographic studies of the mechanisms of sympathetic nerve responses to static exercise in humans. Circ Res 57: 461‐469, 1985.
 363.Marlatt MW, Potter MC, Lucassen PJ, van PH. Running throughout middle‐age improves memory function, hippocampal neurogenesis, and BDNF levels in female C57BL/6J mice. Dev Neurobiol 72: 943‐952, 2012.
 364.Marshall RJ, Schirger A, Shepherd JT. Blood pressure during supine exercise in idiopathic orthostatic hypotension. Circulation 24: 76‐81, 1961.
 365.Martins‐Pinge MC, Becker LK, Garcia MR, Zoccal DB, Neto RV, Basso LS, de Souza HC, Lopes OU. Attenuated pressor responses to amino acids in the rostral ventrolateral medulla after swimming training in conscious rats. Auton Neurosci 122: 21‐28, 2005.
 366.Martins‐Pinge MC, Ponzoni S, Becker LK, Silva CC, Garcia MRL, Lopes OU. Desensitization of arterial pressure response after L‐glutamate microinjection within the rostral ventrolateral medulla of awake rats submitted to swimming training. Soc Neurosci Abstr 26: 823‐823, 2000.
 367.Maskati H, Zbrozyna A. Cardiovascular and motor components of the defense reaction elicited in rats by electrical and chemical stimulation in amygdala. J Auton Nerv Syst 28: 127‐132, 1989.
 368.Massett MP, Lewis SJ, Kregel KC. Effect of heating on the hemodynamic responses to vasoactive agents. Am J Physiol 275: 844‐853, 1998.
 369.Matsukawa K, Mitchell JH, Wall PT, Wilson LB. The effect of static exercise on renal sympathetic nerve activity in conscious cats. J Physiol 434: 453‐467, 1991.
 370.Matsukawa K, Wall PT, Wilson LB, Mitchell JH. Reflex responses of renal nerve activity during isometric muscle contraction in cats. Am J Physiol 259: H1380‐H1388, 1990.
 371.Matsukawa K, Wall PT, Wilson LB, Mitchell JH. Reflex stimulation of cardiac sympathetic nerve activity during static muscle contraction in cats. Am J Physiol 267: 821‐827, 1994.
 372.Mazzeo RS, Rajkumar C, Jennings G, Esler M. Norepinephrine spillover at rest and during submaximal exercise in young and old subjects. J Appl Physiol 82: 1869‐1874, 1997.
 373.McAllister RM. Adaptations in control of blood flow with training: splanchnic and renal blood flows. Med Sci Sports Exerc 30: 375‐381, 1998.
 374.McCloskey DI, Mitchell JH. Reflex cardiovascular and respiratory response originating in exercising muscle. J Physiol (Lond) 224: 173‐186, 1972.
 375.McCord GR, Minson CT. Cutaneous vascular responses to isometric handgrip exercise during local heating and hyperthermia. J Appl Physiol 98: 2011‐2018, 2005.
 376.McGibbon B, Beaumont WV, Strand J, Paletta FX. Thermal regulation in patients after the healing of large deep burns. Plast Reconst Surg 52: 164‐170, 1973.
 377.McGillivray‐Anderson KM, Faber JE. Effect of acidosis on contraction of microvascular smooth muscle by alpha 1‐ and alpha 2‐adrenoceptors. Implications for neural and metabolic regulation. Circ Res 66: 1643‐1657, 1990.
 378.McGillivray‐Anderson KM, Faber JE. Effect of reduced blood flow on alpha 1‐ and alpha 2‐adrenoceptor constriction of rat skeletal muscle microvessels. Circ Res 69: 165‐173, 1991.
 379.McIlveen SA, Hayes SG, Kaufman MP. Both central command and exercise pressor reflex reset carotid sinus baroreflex. Am J Physiol Heart Circ Physiol 280: H1454‐H1463., 2001.
 380.McIntyre C, Savasta M, Walter B, Vitek J. How does deep brain stimulation work? Present understanding and future questions. J Clin Neurophysiol 21: 40‐50, 2004.
 381.McWilliam PN, Yang T, Chen LX. Changes in the baroreceptor reflex at the start of muscle contraction in the decerebrate cat. J Physiol (London) 436: 549‐558, 1991.
 382.Medgett IC, Hicks PE, Langer SZ. Effect of acidosis on alpha 1‐ and alpha 2‐adrenoceptor‐mediated vasoconstrictor responses in isolated arteries. Eur J Pharmacol 135: 443‐447, 1987.
 383.Melcher A, Donald DE. Maintained ability of carotid baroreflex to regulate arterial pressure during exercise. Am J Physiol 241: H838‐H849, 1981.
 384.Mendelowitz D. Advances in parasympathetic control of heart rate and cardiac function. News Physiol Sci 14: 155‐161, 1999.
 385.Meredith IT, Friberg P, Jennings GL, Dewar EM, Fazio VA, Lambert GW, Esler MD. Exercise training lowers resting renal but not cardiac sympathetic activity in humans. Hypertension 18: 575‐582, 1991.
 386.Michael GJ, Priestley JV. Differential expression of the mRNA for the vanilloid receptor subtype 1 in cells of the adult rat dorsal root and nodose ganglia and its downregulation by axotomy. J Neurosci 19: 1844‐1854, 1999.
 387.Michelini LC. Endogenous vasopressin and the central control of heart rate during dynamic exercise. Braz J Med Biol Res 31: 1185‐1195, 1998.
 388.Michelini LC. The NTS and integration of cardiovascular control during exercise in normotensive and hypertensive individuals. Curr Hypertens Rep 9: 214‐221, 2007.
 389.Michelini LC. Oxytocin in the NTS: A new modulator of cardiovascular control during exercise. Ann N Y Acad Sci 940: 206‐220, 2001.
 390.Michelini LC, O'Leary DS, Raven PB, Nobrega AC. Neural control of circulation and exercise: A translational approach disclosing interactions between central command, arterial baroreflex, and muscle metaboreflex. Am J Physiol Heart Circ Physiol 309: H381‐H392, 2015.
 391.Michelini LC, Stern JE. Exercise‐induced neuronal plasticity in central autonomic networks: Role in cardiovascular control. Exp Physiol 94: 947‐960, 2009.
 392.Middlekauff HR, Nitzsche EU, Hoh CK, Hamilton MA, Fonarow GC, Hage A, Moriguchi JD. Exaggerated muscle mechanoreflex control of reflex renal vasoconstriction in heart failure. J Appl Physiol 90: 1714‐1719, 2001.
 393.Middlekauff HR, Nitzsche EU, Nguyen AH, Hoh CK, Gibbs GG. Modulation of renal cortical blood flow during static exercise in humans. Circ Res 80: 62‐68, 1997.
 394.Mihok ML, Murrant CL. Rapid biphasic arteriolar dilations induced by skeletal muscle contraction are dependent on stimulation characteristics. Can J Physiol Pharmacol 82: 282‐287, 2004.
 395.Miki K, Yoshimoto M, Tanimizu M. Acute shifts of baroreflex control of renal sympathetic nerve activity induced by treadmill exercise in rats. J Physiol 548: 313‐322, 2003.
 396.Mischel NA, Llewellyn‐Smith IJ, Mueller PJ. Physical (in)activity‐dependent structural plasticity in bulbospinal catecholaminergic neurons of rat rostral ventrolateral medulla. J Comp Neurol 522: 499‐513, 2014.
 397.Mischel NA, Mueller PJ. (In)activity‐dependent alterations in resting and reflex control of splanchnic sympathetic nerve activity. J Appl Physiol 111: 1854‐1862, 2011.
 398.Mischel NA, Subramanian M, Dombrowski MD, Llewellyn‐Smith IJ, Mueller PJ. (In)activity‐related neuroplasticity in brainstem control of sympathetic outflow: Unraveling underlying molecular, cellular and anatomical mechanisms. Am J Physiol Heart Circ Physiol 309: H235‐H243, 2015.
 399.Mitchell JH. Neural control of the circulation during exercise. Med Sci Sports Exerc 22: 141‐154, 1990.
 400.Mitchell JH, Kaufman MP, Iwamoto GA. The exercise pressor reflex: Its cardiovascular effects, afferent mechanisms, and central pathways. Ann Rev Physiol 45: 229‐242, 1983.
 401.Mitchell JH, Reeves DR, Jr., Rogers HB, Secher NH, Victor RG. Autonomic blockade and cardiovascular responses to static exercise in partially curarized man. J Physiol 413: 433‐445, 1989.
 402.Mitchell JH, Schmidt RF. Cardiovascular reflex control by afferent fibers from skeletal muscle receptors. In: Handbook of Physiology. Bethesda, MD: American Physiological Society, 1988, pp. 623‐658.
 403.Mittelstadt SW, Bell LB, O'Hagan KP, Sulentic JE, Clifford PS. Muscle chemoreflex causes renal vascular constriction. Am J Physiol 270: H951‐H956, 1996.
 404.Mizuno M, Murphy MN, Mitchell JH, Smith SA. Skeletal muscle reflex‐mediated changes in sympathetic nerve activity are abnormal in spontaneously hypertensive rats. Am J Physiol 300: H968‐H977, 2011.
 405.Moffitt JA, Foley CM, Schadt JC, Laughlin MH, Hasser EM. Attenuated baroreflex control of sympathetic nerve activity after cardiovascular deconditioning in rats. Am J Physiol 274: R1397‐R1405, 1998.
 406.Moffitt JA, Grippo AJ, Beltz TG, Johnson AK. Hindlimb unloading elicits anhedonia and sympathovagal imbalance. J Appl Physiol 105: 1049‐1059, 2008.
 407.Moffitt JA, Heesch CM, Hasser EM. Increased GABA(A) inhibition of the RVLM after hindlimb unloading in rats. Am J Physiol Regul Integr Comp Physiol 283: R604‐R614, 2002.
 408.Moffitt JA, Schadt JC, Hasser EM. Altered central nervous system processing of baroreceptor input following hindlimb unloading in rats. Am J Physiol 277: H2272‐H2279, 1999.
 409.Momen A, Bower D, Leuenberger UA, Boehmer J, Lerner S, Alfrey EJ, Handly B, Sinoway LI. Renal vascular response to static handgrip exercise: Sympathetic vs. autoregulatory control. Am J Physiol Heart Circ Physiol 289: H1770‐H1776, 2005.
 410.Momen A, Cui J, McQuillan P, Sinoway LI. Local prostaglandin blockade attenuates muscle mechanoreflex‐mediated renal vasoconstriction during muscle stretch in humans. Am J Physiol Heart Circ Physiol 294: H2184‐H2190, 2008.
 411.Momen A, Leuenberger UA, Ray CA, Cha S, Handly B, Sinoway LI. Renal vascular responses to static handgrip: Role of muscle mechanoreflex. Am J Physiol Heart Circ Physiol 285: H1247‐H1253, 2003.
 412.Moore AW, Jackson WF, Segal SS. Regional heterogeneity of α‐adrenoreceptor subtypes in arteriolar networks of mouse skeletal muscle. J Physiol 588: 4261‐4274, 2010.
 413.Morey‐Holton ER, Globus RK. Hindlimb unloading rodent model: Technical aspects. J Appl Physiol 92: 1367‐1377, 2002.
 414.Morita‐Tsuzuki Y, Hardebo JE, Bouskela E. Inhibition of nitric oxide synthase attenuates the cerebral blood flow response to stimulation of postganglionic parasympathetic nerves in the rat. J Cereb Blood Flow Metab 13: 993‐997, 1993.
 415.Morita‐Tsuzuki Y, Hardebo JE, Bouskela E. Interaction between cerebrovascular sympathetic, parasympathetic and sensory nerves in blood flow regulation. J Vasc Res 30: 263‐271, 1993.
 416.Morrison S, Reis D. Responses of sympathetic preganglionic neurons to rostral ventrolateral medullary stimulation. Am J Physiol 261: R1247‐R1256, 1991.
 417.Morrison SF, Reis DJ. Reticulospinal vasomotor neurons in the RVL mediate the somatosympathetic reflex. Am J Physiol 256: R1084‐R1097, 1989.
 418.Mortensen SP, Gonzalez‐Alonso J, Bune LT, Saltin B, Pilegaard H, Hellsten Y. ATP‐induced vasodilation and purinergic receptors in the human leg: Roles of nitric oxide, prostaglandins, and adenosine. Am J Physiol Regul Integr Comp Physiol 296: R1140‐R1148, 2009.
 419.Mueller PJ. Exercise training and sympathetic nervous system activity: Evidence for physical activity dependent neural plasticity. Clin Exp Pharmacol Physiol 34: 377‐384, 2007.
 420.Mueller PJ. Exercise training attenuates increases in lumbar sympathetic nerve activity produced by stimulation of the rostral ventrolateral medulla. J Appl Physiol (1985) 102: 803‐813, 2007.
 421.Mueller PJ. Influence of sedentary versus physically active conditions on regulation of plasma renin activity and vasopressin. Am J Physiol Regul Integr Comp Physiol 295: 727‐732, 2008.
 422.Mueller PJ. Physical (in)activity‐dependent alterations at the rostral ventrolateral medulla: Influence on sympathetic nervous system regulation. Am J Physiol Regul Integr Comp Physiol 298: R1468‐R1474, 2010.
 423.Mueller PJ, Cunningham JT, Patel KP, Hasser EM. Proposed role of the paraventricular nucleus in cardiovascular deconditioning. Acta Physiol Scand 177: 27‐35, 2003.
 424.Mueller PJ, Foley CM, Heesch CM, Cunningham JT, Zheng H, Patel KP, Hasser EM. Increased nitric oxide synthase activity and expression in the hypothalamus of hindlimb unloaded rats. Brain Res 1115: 65‐74, 2006.
 425.Mueller PJ, Hasser EM. Enhanced sympathoinhibitory response to volume expansion in conscious hindlimb‐unloaded rats. J Appl Physiol (1985) 94: 1806‐1812, 2003.
 426.Mueller PJ, Hasser EM. Putative role of the NTS in alterations in neural control of the circulation following exercise training in rats. Am J Physiol Regul Integr Comp Physiol 290: R383‐R392, 2006.
 427.Mueller PJ, Mischel NA. Selective enhancement of glutamate‐mediated pressor responses after GABA(A) receptor blockade in the RVLM of sedentary versus spontaneous wheel running rats. Front Physiol 3: 447, 2012.
 428.Mueller PJ, O'Hagan KP, Skogg KA, Buckwalter JB, Clifford PS. Renal hemodynamic responses to dynamic exercise in rabbits. J Appl Physiol 85: 1605‐1614, 1998.
 429.Mueller PJ, Sullivan MJ, Grindstaff RR, Cunningham JT, Hasser EM. Regulation of plasma vasopressin and renin activity in conscious hindlimb‐unloaded rats. Am J Physiol Regul Integr Comp Physiol 291: R46‐R52, 2006.
 430.Murphy MN, Mizuno M, Mitchell JH, Smith SA. Cardiovascular regulation by skeletal muscle reflexes in health and disease. Am J Physiol Heart Circ Physiol 301: H1191‐H1204, 2011.
 431.Murrant CL. Stimulation characteristics that determine arteriolar dilation in skeletal muscle. Am J Physiol Regul Integr Comp Physiol 289: R505‐R513, 2005.
 432.Musch TI, Eklund KE, Hageman KS, Poole DC. Altered regional blood flow responses to submaximal exercise in older rats. J Appl Physiol 96: 81‐88, 2004.
 433.N'Diaye A, Sevoz‐Couche C, Nosjean A, Hamon M, Laguzzi R. Stimulation of 5‐HT2 receptors in the nucleus tractus solitarius enhances NMDA receptor‐mediated reflex‐evoked bradycardiac responses in the rat. Auton Neurosci 92: 45‐55, 2001.
 434.Nadel ER, Cafarelli E, Roberts MF, Wenger CB. Circulatory regulation during exercise in different ambient temperatures. J Appl Physiol 46: 430‐437, 1979.
 435.Nadland IH, Walloe L, Toska K. Effect of the leg muscle pump on the rise in muscle perfusion during muscle work in humans. Eur J Appl Physiol 105: 829‐841, 2009.
 436.Naik JS, Valic Z, Buckwalter JB, Clifford PS. Rapid vasodilation in response to a brief tetanic muscle contraction. J Appl Physiol 87: 1741‐1746, 1999.
 437.Negrao C‐E, Irigoyen MC, Moreira ED, Brum P‐C, Freire PM, Krieger E‐M. Effect of exercise training on RSNA, baroreflex control, and blood pressure responsiveness. Am J Physiol Regul Integr Comp Physiol 265: R365‐R370, 1993.
 438.Nelson AJ, Iwamoto GA. Reversibility of exercise‐induced dendritic attenuation in brain cardiorespiratory and locomotor areas following exercise training. J Appl Physiol 101: 1243‐1251, 2006.
 439.Nelson AJ, Juraska JM, Musch TI, Iwamoto GA. Neuroplastic adaptations to exercise: Neuronal remodeling in cardiorespiratory and locomotor areas. J Appl Physiol 99: 2312‐2322, 2005.
 440.Nelson AJ, Juraska JM, Ragan BG, Iwamoto GA. Effects of exercise training on dendritic morphology in the cardiorespiratory and locomotor centers of the mature rat brain. J Appl Physiol 108: 1582‐1590, 2010.
 441.Nelson E, Rennels M. Innervation of intracranial arteries. Brain 93: 475‐490, 1970.
 442.Nelson E, Takayanagi T, Rennels ML, Kawamura J. The innervation of human intracranial arteries: A study by scanning and transmission electron microscopy. J Neuropathol Exp Neurol 31: 526‐534, 1972.
 443.Nielsen B, Davies CT. Temperature regulation during exercise in water and air. Acta Physiol Scand 98: 500‐508, 1976.
 444.Nielsen B, Savard G, Richter EA, Hargreaves M, Saltin B. Muscle blood flow and muscle metabolism during exercise and heat stress. J Appl Physiol 69: 1040‐1046, 1990.
 445.Nielsen KC, Owman C. Adrenergic innervation of pial arteries related to the circle of Willis in the cat. Brain Res 6: 773‐776, 1967.
 446.Nobrega AC, Williamson JW, Friedman DB, Araujo CG, Mitchell JH. Cardiovascular responses to active and passive cycling movements. Med Sci Sports Exerc 26: 709‐714., 1994.
 447.Norton KH, Boushel R, Strange S, Saltin B, Raven PB. Resetting of the carotid arterial baroreflex during dynamic exercise in humans. J Appl Physiol 87: 332‐338, 1999.
 448.Norton KH, Gallagher KM, Smith SA, Querry RG, Welch‐O'Connor RM, Raven PB. Carotid baroreflex function during prolonged exercise. J Appl Physiol 87: 339‐347, 1999.
 449.Nose H, Mack GW, Shi X, Morimoto K, Nadel ER. Effect of saline infusion during exercise on thermal and circulatory regulations. J Appl Physiol 69: 609‐616, 1990.
 450.Nowak M, Holm S, Biering‐Sorensen F, Secher NH, Friberg L. “Central command” and insular activation during attempted foot lifting in paraplegic humans. Hum Brain Mapp 25: 259‐265, 2005.
 451.Nowak M, Olsen KS, Law I, Holm S, Paulson OB, Secher NH. Command‐related distribution of regional cerebral blood flow during attempted handgrip. J Appl Physiol 86: 819‐824, 1999.
 452.Nybo L. Exercise and heat stress: Cerebral challenges and consequences. Prog Brain Res 162: 29‐43, 2007.
 453.Nybo L, Moller K, Volianitis S, Nielsen B, Secher NH. Effects of hyperthermia on cerebral blood flow and metabolism during prolonged exercise in humans. J Appl Physiol 93: 58‐64, 2002.
 454.Nybo L, Nielsen B. Middle cerebral artery blood velocity is reduced with hyperthermia during prolonged exercise in humans. J Physiol 534: 279‐286, 2001.
 455.O'Callaghan RM, Ohle R, Kelly AM. The effects of forced exercise on hippocampal plasticity in the rat: A comparison of LTP, spatial‐ and non‐spatial learning. Behav Brain Res 176: 362‐366, 2007.
 456.O'Hagan K, Bell L, Mittelstadt S, Clifford P. Cardiac receptors modulate the renal sympathetic response to dynamic exercise in rabbits. J Appl Physiol 76: 507‐515, 1994.
 457.O'Hagan KP, Bell LB, Mittelstadt SW, Clifford PS. Effect of dynamic exercise on renal sympathetic nerve activity in conscious rabbits. J Appl Physiol 74: 2099‐2104, 1993.
 458.O'Hagan KP, Casey SM, Clifford PS. Muscle chemoreflex increases renal sympathetic nerve activity during exercise. J Appl Physiol 82: 1818‐1825, 1997.
 459.O'Leary DS. Autonomic mechanisms of muscle metaboreflex control of heart rate. J Appl Physiol 74: 1748‐1754, 1993.
 460.O'Leary DS, Robinson ED, Butler JL. Is active skeletal muscle functionally vasoconstricted during dynamic exercise in conscious dogs? Am J Physiol Regul Integr Comp Physiol 272: R386‐R391, 1997.
 461.Ogoh S. Autonomic control of cerebral circulation: exercise. Med Sci Sports Exerc 40: 2046‐2054, 2008.
 462.Ogoh S, Ainslie PN. Cerebral blood flow during exercise: mechanisms of regulation. J Appl Physiol 107: 1370‐1380, 2009.
 463.Ogoh S, Ainslie PN. Regulatory mechanisms of cerebral blood flow during exercise: New concepts. Exerc Sport Sci Rev 37: 123‐129, 2009.
 464.Ogoh S, Brothers R, Barnes Q, Eubank W, Hawkins M, Purkayastha S, O‐Yurvati A, Raven P. Cardiopulmonary baroreflex is reset during dynamic exercise. J Appl Physiol 100: 51‐59, 2006.
 465.Ogoh S, Brothers RM, Barnes Q, Eubank WL, Hawkins MN, Purkayastha S, A OY, Raven PB. The effect of changes in cardiac output on middle cerebral artery mean blood velocity at rest and during exercise. J Physiol 569: 697‐704, 2005.
 466.Ogoh S, Fadel PJ, Monteiro F, Wasmund WL, Raven PB. Haemodynamic changes during neck pressure and suction in seated and supine positions. J Physiol 540: 707‐716., 2002.
 467.Ogoh S, Fadel PJ, Nissen P, Jans O, Selmer C, Secher NH, Raven PB. Baroreflex‐mediated changes in cardiac output and vascular conductance in response to alterations in carotid sinus pressure during exercise in humans. J Physiol 550: 317‐324., 2003.
 468.Ogoh S, Fisher J, Fadel PJ, Raven PB. Increases in central blood volume modulate carotid baoreflex resetting during dynamic exercise in humans. J Physiol 581: 405‐418, 2007.
 469.Ogoh S, Fisher JP, Raven PB, Fadel PJ. Arterial baroreflex control of muscle sympathetic nerve activity in the transition from rest to steady‐state dynamic exercise in humans. Am J Physiol Heart Circ Physiol 293: H2202‐H2209, 2007.
 470.Ogoh S, Hayashi N, Inagaki M, Ainslie PN, Miyamoto T. Interaction between the ventilatory and cerebrovascular responses to hypo‐ and hypercapnia at rest and during exercise. J Physiol 586: 4327‐4338, 2008.
 471.Ogoh S, Wasmund WL, Keller DM, A OY, Gallagher KM, Mitchell JH, Raven PB. Role of central command in carotid baroreflex resetting in humans during static exercise. J Physiol 543: 349‐364., 2002.
 472.Ohyanagi M, Faber JE, Nishigaki K. Differential activation of alpha 1‐ and alpha 2‐adrenoceptors on microvascular smooth muscle during sympathetic nerve stimulation. Circ Res 68: 232‐244, 1991.
 473.Overton JM. Influence of autonomic blockade on cardiovascular responses to exercise in rats. J Appl Physiol 75: 155‐161, 1993.
 474.Pan HL, Stebbins CL, Longhurst JC. Bradykinin contributes to the exercise pressor reflex: Mechanism of action. J Appl Physiol 75: 2061‐2068, 1993.
 475.Panneton WM, Gan Q, Juric R. The central termination of sensory fibers from nerves to the gastrocnemius muscle of the rat. Neurosci 134: 175‐187, 2005.
 476.Papelier Y, Escourrou P, Gauthier JP, Rowell LB. Carotid baroreflex control of blood pressure and heart rate in men during dynamic exercise. J Appl Physiol 77: 502‐506, 1994.
 477.Patel KP, Zheng H. Central neural control of sympathetic nerve activity in heart failure following exercise training. Am J Physiol Heart Circ Physiol 302: H527‐H537, 2012.
 478.Patil RD, DiCarlo SE, Collins HL. Acute exercise enhances nitric oxide modulation of vascular response to phenylephrine. Am J Physiol 265: 1184‐1188, 1993.
 479.Paton JF, Deuchars J, Ahmad Z, Wong LF, Murphy D, Kasparov S. Adenoviral vector demonstrates that angiotensin II‐induced depression of the cardiac baroreflex is mediated by endothelial nitric oxide synthase in the nucleus tractus solitarii of the rat. J Physiol 531: 445‐458., 2001.
 480.Paulson OB, Strandgaard S, Edvinsson L. Cerebral Autoregulation. Cerebrovasc Brain Metab Rev 2: 161‐192, 1990.
 481.Pawelczyk JA, Raven PB. Reductions in central venous pressure improve carotid baroreflex responses in conscious men. Am J Physiol 257: H1389‐H1395, 1989.
 482.Pérgola PE, Kellogg DL, Jr., Johnson JM, Kosiba WA, Solomon DE. Role of sympathetic nerves in the vascular effects of local temperature in human forearm skin. Am J Physiol 265: H785‐H792, 1993.
 483.Perko MJ, Nielsen HB, Skak C, Clemmesen JO, Schroeder TV, Secher NH. Mesenteric, coeliac and splanchnic blood flow in humans during exercise. J Physiol 513(Pt 3): 907‐913, 1998.
 484.Pernow J, Öhlén A, Hökfelt T, Nilsson O, Lundberg JM. Neuropeptide Y: Presence in perivascular noradrenergic neurons and vasoconstrictor effects on skeletal muscle blood vessels in experimental animals and man. Regul Pept 19: 313‐324, 1987.
 485.Person RJ. Somatic and vagal afferent convergence on solitary tract neurons in cat: Electrophysiological characteristics. Neuroscience 30: 283‐295, 1989.
 486.Peters JH, McDougall SJ, Kellett DO, Jordan D, Llewellyn‐Smith IJ, Andresen MC. Oxytocin enhances cranial visceral afferent synaptic transmission to the solitary tract nucleus. J Neurosci 28: 11731‐11740, 2008.
 487.Peterson DF, Armstrong RB, Laughlin MH. Sympathetic neural influences on muscle blood flow in rats during submaximal exercise. J Appl Physiol 65: 434‐440, 1988.
 488.Phillis JW, Scislo TJ, O'Leary DS. Purines and the nucleus tractus solitarius: Effects on cardiovascular and respiratory function. Clin Exp Pharmacol Physiol 24: 738‐742, 1997.
 489.Pickel VM, Reis DJ, Leeman SE. Ultrastructural localization of substance P in neurons of rat spinal cord. Brain Res 122: 534‐540, 1977.
 490.Pickering TG, Gribbin B, Petersen ES, Cunningham DJ, Sleight P. Effects of autonomic blockade on the baroreflex in man at rest and during exercise. Circ Res 30: 177‐185., 1972.
 491.Pilowsky PM, Goodchild AK. Baroreceptor reflex pathways and neurotransmitters: 10 years on. J Hypertens 20: 1675‐1688, 2002.
 492.Pollak KA, Swenson JD, Vanhaitsma TA, Hughen RW, Jo D, Light KC, Schweinhardt P, Amann M, Light AR. Exogenously applied muscle metabolites synergistically evoke sensations of muscle fatigue and pain in human subjects. Exp Physiol 99: 368‐380, 2014.
 493.Potts JT. Exercise and sensory integration role of the nucleus tractus solitarius. Ann N Y Acad Sci 940: 221‐236, 2001.
 494.Potts JT. Inhibitory neurotransmission in the nucleus tractus solitarii: Implications for baroreflex resetting during exercise. Exp Physiol 91.1: 59‐72, 2006.
 495.Potts JT, Lee SM, Anguelov PI. Tracing of projection neurons from the cervical dorsal horn to the medulla with the antergrade tracer biotinylated dextran amine. Auton Neurosci 98: 64‐69, 2002.
 496.Potts JT, Mitchell JH. Rapid resetting of carotid baroreceptor reflex by afferent input from skeletal muscle receptors. Am J Physiol 275: H2000‐H2008, 1998.
 497.Potts JT, Paton JFR, Mitchell JH, Garry MG, Kline G, Anguelov PT, Lee SM. Contraction‐sensitive skeletal muscle afferents inhibit arterial baroreceptor signalling in the nucleus of the solitary tract: role of intrinsic Gaba interneurons. Neuroscience 119: 201‐214, 2003.
 498.Potts JT, Shi X, Raven PB. Cardiopulmonary baroreceptors modulate carotid baroreflex control of heart rate during dynamic exercise in humans. Am J Physiol 268: H1567‐H1576, 1995.
 499.Potts JT, Shi XR, Raven PB. Carotid baroreflex responsiveness during dynamic exercise in humans. Am J Physiol 265: H1928‐H1938, 1993.
 500.Queme LF, Ross JL, Lu P, Hudgins RC, Jankowski MP. Dual modulation of nociception and cardiovascular reflexes during peripheral ischemia through P2Y1 receptor‐dependent sensitization of muscle afferents. J Neurosci 36: 19‐30, 2016.
 501.Querry RG, Smith SA, Stromstad M, Ide K, Raven PB, Secher NH. Neural blockade during exercise augments central command's contribution to carotid baroreflex resetting. Am J Physiol 280: H1635‐H1644, 2001.
 502.Ralevic V, Burnstock G. Postjunctional synergism of noradrenaline and adenosine 5′‐triphosphate in the mesenteric arterial bed of the rat. Eur J Pharmacol 175: 291‐299, 1990.
 503.Rasmussen P, Stie H, Nielsen B, Nybo L. Enhanced cerebral CO(2) reactivity during strenuous exercise in man. Eur J Appl Physiol 1‐6, 2006.
 504.Raven PB, Fadel PJ, Ogoh S. Arterial baroreflex resetting during exercise: A current perspective. Exp Physiol 91: 37‐49, 2006.
 505.Raven PB, Potts JT, Shi X. Baroreflex regulation of blood pressure during dynamic exercise. Exerc Sport Sci Rev 25: 365‐389, 1997.
 506.Ray CA, Hume KM. Sympathetic neural adaptation to exercise training in humans: Insights from microneurography. Med Sci Sports Exerc 30: 387‐391, 1998.
 507.Ray CA, Rea RF, Clary MP, Mark AL. Muscle sympathetic nerve responses to dynamic one‐legged exercise: Effect of body posture. Am J Physiol 264: H1‐H7., 1993.
 508.Rehrer NJ, Smets A, Reynaert H, Goes E, De Meirleir K. Effect of exercise on portal vein blood flow in man. Med Sci Sports Exerc 33: 1533‐1537, 2001.
 509.Reidman DA, Maher TJ, Chaiyakul P, Ally A. Modulation of extracellular glutamate and pressor response to muscle contraction during NMDA‐receptor blockade in the rostral ventrolateral medulla. Neurosci Res 36: 147‐156, 2000.
 510.Rein H. Die Interferenz der vasomotorischen Regulationen. Klin Wchnschr 9: 1485, 1930.
 511.Remensnyder JP, Mitchell JH, Sarnoff SJ. Functional sympatholysis during muscular activity. Observations on influence of carotid sinus on oxygen uptake. Circ Res 11: 370‐380, 1962.
 512.Revington M, McCloskey DI. Neuropeptide Y and control of vascular resistance in skeletal muscle. Regul Pept 23: 331‐342, 1988.
 513.Ricksten SE, Thoren P. Reflex control of sympathetic nerve activity and heart rate from arterial baroreceptors in conscious spontaneously hypertensive rats. Clin Sci (Lond) 61(Suppl 7): 169s‐172s, 1981.
 514.Ricksten SE, Thoren P. Reflex inhibition of sympathetic activity during volume load in awake normotensive and spontaneously hypertensive rats. Acta Physiol Scand 110: 77‐82, 1980.
 515.Ringelstein EB, Van Eyck S, Mertens I. Evaluation of cerebral vasomotor reactivity by various vasodilating stimuli: comparison of CO2 to acetazolamide. J Cereb Blood Flow Metab 12: 162‐168, 1992.
 516.Roddie IC. Circulation to skin and adipose tissue. In: Shepherd JT, Abboud FM, editors. Handbook of Physiology: The Cardiovascular System Section 2, The Cardiovascular System. Bethesda, MD: American Physiological Society, 1983, pp. 285‐317.
 517.Roddie IC, Shepherd JT. The reflex nervous control of human skeletal muscle blood vessels. Clin Sci (Lond) 15: 433‐440, 1956.
 518.Roddie IC, Shepherd JT, Whelan RF. The contribution of constrictor and dilator nerves to the skin vasodilation during body heating. J Physiol London 136: 489‐497, 1957.
 519.Roddie IC, Shepherd JT, Whelan RF. The vasomotor nerve supply to the skin and muscle of the human forearm. Clin Sci (Lond) 16: 67‐74, 1956.
 520.Rongen GA, Lenders JWM, Lambrou J, Willemsen JJ, Van Belle H, Thien T, Smits P. Presynaptic inhibition of norepinephrine release from sympathetic nerve endings by endogenous adenosine. Hypertension 27: 933‐938, 1996.
 521.Rosenmeier JB, Dinenno FA, Fritzlar SJ, Joyner MJ. alpha1‐ and alpha2‐adrenergic vasoconstriction is blunted in contracting human muscle. J Physiol 547: 971‐976, 2003.
 522.Rosenmeier JB, Hansen J, Gonzalez‐Alonso J. Circulating ATP‐induced vasodilatation overrides sympathetic vasoconstrictor activity in human skeletal muscle. J Physiol 558: 351‐365, 2004.
 523.Rosenmeier JB, Yegutkin GG, Gonzalez‐Alonso J. Activation of ATP/UTP‐selective receptors increases blood flow and blunts sympathetic vasoconstriction in human skeletal muscle. J Physiol 586: 4993‐5002, 2008.
 524.Ross CA, Ruggiero DA, Joh TH, Park DH, Reis DJ. Rostral ventrolateral medulla: Selective projections to the thoracic autonomic cell column from the region containing C1 adrenaline neurons. J Comp Neurol 228: 168‐185, 1984.
 525.Ross CA, Ruggiero DA, Park DH, Joh TH, Sved AF, Fernandez‐Pardal J, Saavedra JM, Reis DJ. Tonic vasomotor control by the rostral ventrolateral medulla: Effect of electrical or chemical stimulation of the area containing C1 adrenaline neurons on arterial pressure, heart rate, and plasma catecholamines and vasopressin. J Neurosci 4: 474‐494, 1984.
 526.Rotto DM, Hill JM, Schultz HD, Kaufman MP. Cyclooxygenase blockade attenuates the responses of group IV muscle afferents to static contraction. Am J Physiol 259: H745‐H750, 1990.
 527.Rotto DM, Kaufman MP. Effect of metabolic products of muscular contraction on discharge of group III and IV afferents. J Appl Physiol 64: 2306‐2313, 1988.
 528.Rotto DM, Schultz HD, Longhurst JC, Kaufman MP. Sensitization of group III muscle afferents to static contraction by products of arachidonic acid metabolism. J Appl Physiol 68: 861‐867, 1990.
 529.Roveda F, Middlekauff HR, Rondon MU, Reis SF, Souza M, Nastari L, Barretto AC, Krieger EM, Negrao CE. The effects of exercise training on sympathetic neural activation in advanced heart failure: A randomized controlled trial. J Am Coll Cardiol 42: 854‐860, 2003.
 530.Rowell LB. Control of regional blood flow during dynamic exercise. In: Human Cardiovascular Control. New York: Oxford University Press, 1993, pp. 204‐254.
 531.Rowell LB. Human cardiovascular adjustments to exercise and thermal stress. Physiol Rev 54: 75‐159, 1974.
 532.Rowell LB. Neural control of muscle blood flow: Importance during dynamic exercise. Clin Exp Pharmacol Physiol 24: 117‐125, 1997.
 533.Rowell LB. Regulation of splanchnic blood flow in man. Physiologist 16: 127‐142, 1973.
 534.Rowell LB. Thermal Stress. In: Human Circulation Regulation During Physical Stress. New York: Oxford University Press, 1986, pp. 174‐212.
 535.Rowell LB, Blackmon JR, Bruce RA. Indocyanine green clearance and estimated hepatic blood flow during mild to maximal exercise in upright man. J Clin Invest 43: 1677‐1690, 1964.
 536.Rowell LB, Blackmon JR, Martin RH, Mazzarella JA, Bruce RA. Hepatic clearance of indocyanine green in man under thermal and exercise stresses. J Appl Physiol 20: 384‐394, 1965.
 537.Rowell LB, Brengelmann GL, Murray JA. Cardiovascular responses to sustained high skin temperature in resting man. J Appl Physiol 27: 673‐680, 1969.
 538.Rowell LB, Murray JA, Brengelmann GL, Kraning KK, II. Human cardiovascular adjustments to rapid changes in skin temperature during exercise. Circ Res 24: 711‐724, 1969.
 539.Rowell LB, O'Leary DS, Kellogg DL, Jr. Integration of cardiovascular control systems in dynamic exercise. In: Rowell LB, Shepherd JT, editors. Handbook of Physiology; Exercise: Regulation and integration of multiple systems. Bethesda, MD: American Physiological Society, 1996, pp. 770‐838.
 540.Rowell LB, Saltin B, Kiens B, Christensen NJ. Is peak quadriceps blood flow in humans even higher during exercise with hypoxemia? Am J Physiol 251: H1038‐H1044, 1986.
 541.Roy CS, Sherrington CS. On the regulation of the blood‐supply of the brain. J Physiol 11: 85‐158, 1890.
 542.Ruble SB, Valic Z, Buckwalter JB, Tschakovsky ME, Clifford PS. Attenuated vascular responsiveness to noradrenaline release during dynamic exercise in dogs. J Physiol 541: 637‐644, 2002.
 543.Ruffolo RR, Nichols AJ, Stadel JM, Hieble JP. Structure and function of alpha‐adrenoceptors. Pharmacol Rev 43: 475‐505, 1991.
 544.Rummery NM, Brock JA, Pakdeechote P, Ralevic V, Dunn WR. ATP is the predominant sympathetic neurotransmitter in rat mesenteric arteries at high pressure. J Physiol 582: 745‐754, 2007.
 545.Saad AR, Stephens DP, Bennett LA, Charkoudian N, Kosiba WA, Johnson JM. Influence of isometric exercise on blood flow and sweating in glabrous and nonglabrous human skin. J Appl Physiol 91: 2487‐2492, 2001.
 546.Sagawa K. Baroreflex control of systemic arterial pressure and vascular bed. In: Handbook of Physiology the Cardiovascular System. Bethesda, MD: American Physiological Society, 1983, pp. 453‐496.
 547.Saito M, Naito M, Mano T. Different responses in skin and muscle sympathetic nerve activity to static muscle contraction. J Appl Physiol 69: 2085‐2090, 1990.
 548.Saito M, Tsukanaka A, Yanagihara D, Mano T. Muscle sympathetic nerve responses to graded leg cycling. J Appl Physiol 75: 663‐667., 1993.
 549.Sander M, Macefield VG, Henderson LA. Cortical and brain stem changes in neural activity during static handgrip and postexercise ischemia in humans. J Appl Physiol 108: 1691‐1700, 2010.
 550.Sanders J, Ferguson D. Cardiopulmonary baroreflexes fail to modulate sympathetic responses during isometric exercise in humans: Direct evidence from microneurographic studies. J Am Coll Cardiol 12: 1241‐1251, 1988.
 551.Sanders JS, Mark AL, Ferguson DW. Evidence for cholinergically mediated vasodilation at the beginning of isometric exercise in humans. Circulation 79: 815‐824, 1989.
 552.Saper C. Convergence of autonomic and limbic connections in the insular cortex of the rat. J Comp Neurol 210: 163‐173, 1982.
 553.Sapru HN. Neurotransmitters in the nucleus tractus solitarius mediating cardiovascular function. In: Dun NJ, Machado BH, Pilowsky PM, editors. Neural Mechanisms of Cardiovascular Regulation. Norwell, MA: Kluwer Academic Publishers, 2004, p. 81‐98.
 554.Sato A, Sato Y. Cholinergic neural regulation of regional cerebral blood flow. Alzheimer Dis Assoc Disord 9: 28‐38, 1995.
 555.Saunders NR, Tschakovsky ME. Evidence for a rapid vasodilatory contribution to immediate hyperemia in rest‐to‐mild and mild‐to‐moderate forearm exercise transitions in humans. J Appl Physiol 97: 1143‐1151, 2004.
 556.Savard G, Strange S, Kiens B, Richter EA, Christensen NJ, Saltin B. Noradrenaline spillover during exercise in active versus resting skeletal muscle in man. Acta Physiol Scand 131: 507‐515, 1987.
 557.Savard GK, Nielsen B, Laszczynska J, Larsen BE, Saltin B. Muscle blood flow is not reduced in humans during moderate exercise and heat stress. J Appl Physiol 64: 649‐657, 1988.
 558.Savard GK, Richter EA, Strange S, Kiens B, Christensen NJ, Saltin B. Norepinephrine spillover from skeletal muscle during exercise in humans: Role of muscle mass. Am J Physiol 257: 1812‐1818, 1989.
 559.Sawasaki N, Iwase S, Mano T. Effect of skin sympathetic response to local or systemic cold exposure on thermoregulatory functions in humans. Auton Neurosci 87: 274‐281, 2001.
 560.Scherrer U, Floistrup S, Vissing S, Victor RG. Effect of lower body negative pressure on sympathetic nerve responses to static exercise in humans. Circulation 78: 49‐59, 1988.
 561.Scherrer U, Pryor SL, Bertocci LA, Victor RG. Arterial baroreflex buffering of sympathetic activation during exercise‐induced elevations in arterial pressure. J Clin Invest 86: 1855‐1861, 1990.
 562.Schlader ZJ, Ganio MS, Pearson J, Lucas RA, Gagnon D, Rivas E, Kowalske KJ, Crandall CG. Heat acclimation improves heat exercise tolerance and heat dissipation in individuals with extensive skin grafts. J Appl Physiol (1985) 119: 69‐76, 2015.
 563.Schlader ZJ, Seifert T, Wilson TE, Bundgaard‐Nielsen M, Secher NH, Crandall CG. Acute volume expansion attenuates hyperthermia‐induced reductions in cerebral perfusion during simulated hemorrhage. J Appl Physiol 114: 1730‐1735, 2013.
 564.Schneider AG, Goodwin MD, Bellomo R. Measurement of kidney perfusion in critically ill patients. Crit Care 17: 220, 2013.
 565.Schreihofer AM, Sved AF. The ventrolateral medulla and sympathetic regulation of arterial pressure. In: Llewellyn‐Smith IJ, Verberne AJM, editors. Autonomic Control of Cardiovascular Function. New York: Oxford University Press, 2011, pp. 78‐97.
 566.Schuerch LV, Linder LM, Grouzmann E, Haefeli WE. Human neuropeptide Y potentiates alpha 1‐adrenergic blood pressure responses in vivo. Am J Physiol Heart Circ Physiol 275: H760‐H766, 1998.
 567.Seagard JL, Dean C, Hopp FA. Neurochemical transmission of baroreceptor input in the nucleus tractus solitarius. Brain Res Bull 51: 111‐118, 2000.
 568.Seals DR. Cardiopulmonary baroreflexes do not modulate exercise‐induced sympathoexcitation. J Appl Physiol 64: 2197‐2203, 1988.
 569.Seals DR, Victor RG. Regulation of muscle sympathetic nerve activity during exercise in humans. Exerc Sport Sci Rev 19: 313‐349, 1991.
 570.Seals DR, Victor RG, Mark AL. Plasma norepinephrine and muscle sympathetic discharge during rhythmic exercise in humans. J Appl Physiol 65: 940‐944, 1988.
 571.Secher NH, Kjaer M, Galbo H. Arterial blood pressure at the onset of dynamic exercise in partially curarized man. Acta Physiol Scand 133: 233‐237., 1988.
 572.Secher NH, Seifert T, Van Lieshout JJ. Cerebral blood flow and metabolism during exercise: Implications for fatigue. J Appl Physiol 104: 306‐314, 2008.
 573.Seifert T, Fisher JP, Young CN, Hartwich D, Ogoh S, Raven PB, Fadel PJ, Secher NH. Glycopyrrolate abolishes the exercise‐induced increase in cerebral perfusion in humans. Exp Physiol 95: 1016‐1025, 2010.
 574.Seifert T, Secher NH. Sympathetic influence on cerebral blood flow and metabolism during exercise in humans. Prog Neurobiol 95: 406‐426, 2011.
 575.Semenza JC, McCullough JE, Flanders WD, McGeehin MA, Lumpkin JR. Excess hospital admissions during the July 1995 heat wave in Chicago [see comments]. Am J Prev Med 16: 269‐277, 1999.
 576.Serrador JM, Picot PA, Rutt BK, Shoemaker JK, Bondar RL. MRI measures of middle cerebral artery diameter in conscious humans during simulated orthostasis. Stroke 31: 1672‐1678, 2000.
 577.Seylaz J, Hara H, Pinard E, Mraovitch S, MacKenzie ET, Edvinsson L. Effect of stimulation of the sphenopalatine ganglion on cortical blood flow in the rat. J Cereb Blood Flow Metab 8: 875‐878, 1988.
 578.Sheehan D, Mulholland JH, Safiroff B. Surgical anatomy of the carotid sinus nerve. Anat Rec 8o: 431‐442, 1941.
 579.Shekhar A, DiMicco J. Defense reaction elicited by injection of GABA antagonists and synthesis inhibitors into the posterior hypothalamus in rats. Neuropharmacology 26: 407‐417, 1987.
 580.Shepherd JT. Intrathoracic baroreflexes. Mayo Clin Proc 48: 426‐437, 1973.
 581.Shepherd JT. Reflex control of arterial blood pressure. Cardiovasc Res 16: 357‐370, 1982.
 582.Sheriff DD, Rowell LB, Scher AM. Is rapid rise in vascular conductance at onset of dynamic exercise due to muscle pump? Am J Physiol 265: 1227‐1234, 1993.
 583.Shi X, Crandall CG, Potts JT, Foresman BH, Raven PB. A diminished aortic‐cardiac reflex during hypotension in aerobically fit young men. Med Sci Sports Exerc 25: 1024‐1030, 1993.
 584.Shibasaki M, Crandall CG. Mechanisms and controllers of eccrine sweating in humans. Front Biosci (Schol Ed) 2: 685‐696, 2010.
 585.Shibasaki M, Konda N, Crandall CG. Non‐thermoregulatory modulation of sweating in humans. Exerc Sport Sci Rev 31: 34‐39, 2003.
 586.Shibasaki M, Rasmussen P, Secher NH, Crandall CG. Neural and non‐neural control of skin blood flow during isometric handgrip exercise in the heat stressed human. J Physiol 587: 2101‐2107, 2009.
 587.Shibasaki M, Secher NH, Johnson JM, Crandall CG. Central command and the cutaneous vascular response to isometric exercise in heated humans. J Physiol 565: 667‐673, 2005.
 588.Shibasaki M, Secher NH, Selmer C, Kondo N, Crandall CG. Central command is capable of modulating sweating from non‐glabrous human skin. J Physiol 553: 999‐1004, 2003.
 589.Shibasaki M, Wilson TE, Crandall CG. Neural control and mechanisms of eccrine sweating during heat stress and exercise. J Appl Physiol 100: 1692‐1701, 2006.
 590.Shibasaki M, Wilson TE, Cui J, Levine BD, Crandall CG. Exercise throughout 6 degrees head‐down tilt bed rest preserves thermoregulatory responses. J Appl Physiol 95: 1817‐1823, 2003.
 591.Shoemaker JK, Badrov MB, Al‐Khazraji BK, Jackson DN. Neural control of vascular function in skeletal muscle. Compr Physiol 6: 303‐329, 2016.
 592.Shoemaker JK, Tschakovsky ME, Hughson RL. Vasodilation contributes to the rapid hyperemia with rhythmic contractions in humans. Can J Physiol Pharmacol 76: 418‐427, 1998.
 593.Silva AQ, Schreihofer AM. Altered sympathetic reflexes and vascular reactivity in rats after exposure to chronic intermittent hypoxia. J Physiol 589: 1463‐1476, 2011.
 594.Sinoway LI, Hill JM, Pickar JG, Kaufman MP. Effects of contraction and lactic acid on the discharge of group III muscle afferents in cats. J Neurophysiol 69: 1053‐1059, 1993.
 595.Sinoway LI, Smith MB, Enders B, Leuenberger U, Dzwonczyk T, Gray K, Whisler S, Moore RL. Role of diprotanated phosphate in evoking muscle reflex responses in cats and humans. Am J Physiol 267: H770‐H778, 1994.
 596.Sinoway LI, Wroblewski KJ, Prophet SA, Ettinger SM, Gray KS, Whisler SK, Miller G, Moore RL. Glycogen depletion‐induced lactate reductions attenuate reflex responses in exercising humans. Am J Physiol 263: H1499‐H1505, 1992.
 597.Smith CJ, Johnson JM. Responses to hyperthermia. Optimizing heat dissipation by convection and evaporation: Neural control of skin blood flow and sweating in humans. Auton Neurosci 196: 25‐36, 2016.
 598.Smith FG. Techniques for recording renal sympathetic nerve activity in awake, freely moving animals. Methods 30: 122‐126, 2003.
 599.Smith GD, Watson LP, Pavitt DV, Mathias CJ. Abnormal cardiovascular and catecholamine responses to supine exercise in human subjects with sympathetic dysfunction. J Physiol 484(Pt 1): 255‐265, 1995.
 600.Smith JK, Barron KW. GABAergic responses in ventrolateral medulla in spontaneously hypertensive rats. Am J Physiol 258: R450‐R456, 1990.
 601.Smith SA, Leal AK, Murphy MN, Downey RM, Mizuno M. Muscle mechanoreflex overactivity in hypertension: A role for centrally‐derived nitric oxide. Auto Neurosci 188: 58‐63, 2015.
 602.Smith SA, Leal AK, Williams MA, Murphy MN, Mitchell JH, Garry MG. The TRPV1 receptor is a mediator of the exercise pressor reflex in rats. J Physiol 599.7: 1179‐1189, 2010.
 603.Smith SA, Mammen PPA, Mitchell JH, Garry MG. Role of the exercise pressor reflex in rats with dilated cardiomyopathy. Circulation 108: 1126‐1132, 2003.
 604.Smith SA, Mitchell JH, Garry MG. Electrically induced static exercise elicits a pressor response in the decerebrate rat. J Physiol 537: 961‐970, 2001.
 605.Smith SA, Mitchell JH, Garry MG. The mammalian exercise pressor reflex in health and disease. Exp Physiol 91: 89‐102, 2006.
 606.Smith SA, Mitchell JH, Li J. Independent modification of baroreceptor and exercise pressor reflex function by nitric oxide in nucleus tractus solitarius. Am J Physiol 288: H2068‐H2076, 2005.
 607.Smith SA, Mitchell JH, Naseem RH, Garry MG. Mechanoreflex mediates the exaggerated exercise pressor reflex in heart failure. Circulation 112: 2293‐2300, 2005.
 608.Smith SA, Querry RG, Fadel PJ, Gallagher KM, Stromstad M, Ide K, Raven PB, Secher NH. Partial blockade of skeletal muscle somatosensory afferents attenuates baroreflex resetting during exercise in humans. J Physiol 551: 1013‐1021, 2003.
 609.Smith SA, Williams MA, Leal AK, Mitchell JH, Garry MG. Exercise pressor reflex function is altered in spontaneously hypertensive rats. J Physiol 577: 1009‐1020, 2006.
 610.Smith SA, Williams MA, Mitchell JH, Mammen PP, Garry MG. The capsaicin‐sensitive afferent neuron in skeletal muscle is abnormal in heart failure. Circulation 111: 2056‐2065, 2005.
 611.Sokolnicki LA, Strom NA, Roberts SK, Kingsley‐Berg SA, Basu A, Charkoudian N. Skin blood flow and nitric oxide during body heating in type 2 diabetes mellitus. J Appl Physiol 106: 566‐570, 2009.
 612.Soya H, Mukai A, Deocaris C, Ohiwa N, Chang H, Nishijima T, Fujikawa T, Togashi K, Saito T. Threshold‐like pattern of neuronal activation in the hypothalamus during treadmill running: Establishment of a minimum running stress (MRS) rat model. Neurosci Res 58: 341‐348, 2007.
 613.Sprangers RL, Wesseling KH, Imholz AL, Imholz BP, Wieling W. Initial blood pressure fall on stand up and exercise explained by changes in total peripheral resistance. J Appl Physiol 70: 523‐530., 1991.
 614.Stebbins CL, Bonigut S. Endogenous bradykinin in the thoracic spinal cord contributes to the exercise pressor reflex. J Appl Physiol 81: 1288‐1294, 1996.
 615.Stebbins CL, Bonigut S. Spinal angiotensin II influences reflex cardiovascular responses to muscle contraction. Am J Physiol 269: R864‐R868, 1995.
 616.Stebbins CL, Brown B, Levin D, Longhurst JC. Reflex effects of skeletal muscle mechanoreceptor stimulation on the cardiovascular system. J Appl Physiol 65: 1539‐1547, 1988.
 617.Stebbins CL, Ortiz‐Acevedo A. The exercise pressor reflex is attenuated by intrathecal oxytocin. Am J Physiol 267: R909‐R915, 1994.
 618.Stebbins CL, Symons JD. Role of angiotensin II in hemodynamic responses to dynamic exercise in miniswine. J Appl Physiol 78: 185‐190, 1995.
 619.Stebbins CL, Symons JD. Vasopressin contributes to the cardiovascular response to dynamic exercise. Am J Physiol 264: H1701‐H1707, 1993.
 620.Stephens DP, Aoki K, Kosiba WA, Johnson JM. Nonnoradrenergic mechanism of reflex cutaneous vasoconstriction in men. Am J Physiol Heart Circ Physiol 280: H1496‐H1504., 2001.
 621.Stewart JM, Montgomery LD, Glover JL, Medow MS. Changes in regional blood volume and blood flow during static handgrip. Am J Physiol Heart Circ Physiol 292: H215‐H223, 2007.
 622.Stickland MK, Miller JD, Smith CA, Dempsey JA. Carotid chemoreceptor modulation of regional blood flow distribution during exercise in health and chronic heart failure. Circ Res 100: 1371‐1378, 2007.
 623.Stone AJ, Copp SW, Kaufman MP. Role played by NaV 1.7 channels on thin‐fiber muscle afferents in transmitting the exercise pressor reflex. Am J Physiol 309: R1301‐R1308, 2015.
 624.Stone AJ, Copp SW, Kim JS, Kaufman MP. Combined, but not individual, blockade of ASIC3, P2X, and EP4 receptors attenuates the exercise pressor reflex in rats with freely perfused hindlimb muscles. J Appl Physiol 119: 1330‐1336, 2015.
 625.Stornetta RL, Morrison SF, Ruggiero DA, Reis DJ. Neurons of rostral ventrolateral medulla mediate somatic pressor reflex. Am J Physiol 256: R448‐R462, 1989.
 626.Strandgaard S, Sigurdsson ST. Point:Counterpoint: Sympathetic activity does/does not influence cerebral blood flow. Counterpoint: Sympathetic nerve activity does not influence cerebral blood flow. J Appl Physiol 105: 1364‐1368, 2008.
 627.Strange S, Secher NH, Pawelczyk JA, Karpakka J, Christensen NJ, Mitchell JH, Saltin B. Neural control of cardiovascular responses and of ventilation during dynamic exercise in man. J Physiol 470: 693‐704, 1993.
 628.Subramanian M, Holt AG, Mueller PJ. Physical activity correlates with glutamate receptor gene expression in spinally‐projecting RVLM neurons: A laser capture microdissection study. Brain Res 1585: 51‐62, 2014.
 629.Subramanian M, Mueller PJ. Altered differential control of sympathetic outflow following sedentary conditions: Role of subregional neuroplasticity in the RVLM. Front Physiol 7: 290, 2016.
 630.Suzuki M, Kuramochi T, Suga T. GABA receptor subtypes involved in the neuronal mechanisms of baroreceptor reflex in the nucleus tractus solitarii of rabbits. J Auton Nerv Syst 43: 27‐35, 1993.
 631.Suzuki N, Hardebo JE, Kahrstrom J, Owman C. Selective electrical stimulation of postganglionic cerebrovascular parasympathetic nerve fibers originating from the sphenopalatine ganglion enhances cortical blood flow in the rat. J Cereb Blood Flow Metab 10: 383‐391, 1990.
 632.Sved AF, Ito S, Sved JC. Brainstem mechanisms of hypertension: Role of the rostral ventrolateral medulla. Curr Hypertens Rep 5: 262‐268, 2003.
 633.Sved AF, Tsukamoto K. Tonic stimulation of GABAB receptors in the nucleus tractus solitarius modulates the baroreceptor reflex. Brain Res 592: 37‐43, 1992.
 634.Sved AF, Tsukamoto K, Schreihofer AM. Stimulation of alpha 2‐adrenergic receptors in nucleus tractus solitarius is required for the baroreceptor reflex. Brain Res 576: 297‐303, 1992.
 635.Swanson LW, Kuypers HGJM. The paraventricular nucleus of the hypothalamus: Cytoarchitectonic subdivisions and organization of projections to the pituitary, dorsal vagal complex, and spinal cord documented by retrograde fluorescence double‐labeling methods. J Comp Neurol 194: 555‐570, 1980.
 636.Takemoto Y. Depressor and bradycardic actions of L‐proline injected into the nucleus tractus solitarii of anesthetized rats. Jap J Physiol 51: 687‐692, 2001.
 637.Takeshita A, Mark AL, Eckberg DL, Abboud FM. Effect of central venous pressure on arterial baroreflex control of heart rate. Am J Physiol 236: H42‐H47, 1979.
 638.Tallarida G, Baldoni F, Peruzzi G, Brindisi F, Raimondi G, Sangiorgi M. Cardiovascular and respiratory chemoreflexes from the hindlimb sensory receptors evoked by intra‐arterial injection of bradykinin and other chemical agents in the rabbit. J Pharmacol Exp Ther 208: 319‐329, 1979.
 639.Tallarida G, Peruzzi G, Raimondi G. The role of chemosensitive muscle receptors in cardiorespiratory regulation during exercise. J Auton Nerv Syst 30(Suppl): S155‐161, 1990.
 640.Tateishi J, Faber JE. ATP‐sensitive K+ channels mediate {alpha}2D‐adrenergic receptor contraction of arteriolar smooth muscle and reversal of contraction by hypoxia. Circ Res 76: 53‐63, 1995.
 641.Tateishi J, Faber JE. Inhibition of arteriole alpha 2‐ but not alpha 1‐adrenoceptor constriction by acidosis and hypoxia in vitro. Am J Physiol Heart Circ Physiol 268: H2068‐H2076, 1995.
 642.Taylor NAS. Human heat adaptation. Compr Physiol 4: 325‐365, 2014.
 643.Taylor WF, Johnson JM, Kosiba WA. Roles of absolute and relative load in skin vasoconstrictor responses to exercise. J Appl Physiol 69: 1131‐1136, 1990.
 644.Taylor WF, Johnson JM, Kosiba WA, Kwan CM. Cutaneous vascular responses to isometric handgrip exercise. J Appl Physiol 66: 1586‐1592, 1989.
 645.Taylor WF, Johnson JM, Kosiba WA, Kwan CM. Graded cutaneous vascular responses to dynamic leg exercise. J Appl Physiol 64: 1803‐1809, 1988.
 646.ter Laan M, van Dijk JM, Elting JW, Staal MJ, Absalom AR. Sympathetic regulation of cerebral blood flow in humans: A review. Br J Anaesth 111: 361‐367, 2013.
 647.ter Steege RW, Kolkman JJ. Review article: The pathophysiology and management of gastrointestinal symptoms during physical exercise, and the role of splanchnic blood flow. Aliment Pharmacol Ther 35: 516‐528, 2012.
 648.Thomas GD, Hansen J, Victor RG. ATP‐sensitive potassium channels mediate contraction‐induced attenuation of sympathetic vasoconstriction in rat skeletal muscle. J Clin Invest 99: 2602‐2609, 1997.
 649.Thomas GD, Hansen J, Victor RG. Inhibition of a2 ‐adrenergic vasoconstriction during contraction of glycolytic, not oxidative, rat hindlimb muscle. Am J Physiol 266: H920‐H929, 1994.
 650.Thomas GD, Sander M, Lau KS, Huang PL, Stull JT, Victor RG. Impaired metabolic modulation of alpha‐adrenergic vasoconstriction in dystrophin‐deficient skeletal muscle. Proc Natl Acad Sci U S A 95: 15090‐15095, 1998.
 651.Thomas GD, Victor RG. Nitric oxide mediates contraction‐induced attenuation of sympathetic vasoconstriction in rat skeletal muscle. J Physiol 506: 817‐826, 1998.
 652.Thomas SN, Schroeder T, Secher NH, Mitchell JH. Cerebral blood flow during submaximal and maximal dynamic exercise in humans. J Appl Physiol 67: 744‐748, 1989.
 653.Thornton JM, Guz A, Murphy K, Griffith AR, Pedersen DL, Kardos A, Leff A, Adams L, Casadei B, Paterson DJ. Identification of higher brain centres that may encode the cardiorespiratory response to exercise in humans. J Physiol 533: 823‐836, 2001.
 654.Tidgren B, Hjemdahl P, Theodorsson E, Nussberger J. Renal neurohormonal and vascular responses to dynamic exercise in humans. J Appl Physiol 70: 2279‐2286, 1991.
 655.Timmers HJ, Karemaker JM, Wieling W, Marres HA, Lenders JW. Baroreflex control of muscle sympathetic nerve activity after carotid body tumor resection. Hypertension 42: 143‐149., 2003.
 656.Toda N, Ayajiki K, Tanaka T, Okamura T. Preganglionic and postganglionic neurons responsible for cerebral vasodilation mediated by nitric oxide in anesthetized dogs. J Cereb Blood Flow Metab 20: 700‐708, 2000.
 657.Tschakovsky ME, Hughson RL. Rapid blunting of sympathetic vasoconstriction in the human forearm at the onset of exercise. J Appl Physiol 94: 1785‐1792, 2003.
 658.Tschakovsky ME, Rogers AM, Pyke KE, Saunders NR, Glenn N, Lee SJ, Weissgerber T, Dwyer EM. Immediate exercise hyperemia in humans is contraction intensity dependent: Evidence for rapid vasodilation. J Appl Physiol 96: 639‐644, 2004.
 659.Tschakovsky ME, Shoemaker JK, Hughson RL. Vasodilation and muscle pump contribution to immediate exercise hyperemia. Am J Physiol Heart Circ Physiol 271: H1697‐H1701, 1996.
 660.Tschakovsky ME, Sujirattanawimol K, Ruble SB, Valic Z, Joyner MJ. Is sympathetic neural vasoconstriction blunted in the vascular bed of exercising human muscle? J Physiol 541: 623‐635, 2002.
 661.Tsuchimochi H, Matsukawa K, Komine H, Murata J. Direct measurement of cardiac sympathetic efferent nerve activity during dynamic exercise. Am J Physiol Heart Circ Physiol 283: H1896‐H1906, 2002.
 662.Uvnas B. Cholinergic vasodilator nerves. Federation Proc 1613‐1622, 1966.
 663.Valic Z, Buckwalter JB, Clifford PS. Muscle blood flow response to contraction: influence of venous pressure. J Appl Physiol 98: 72‐76, 2005.
 664.van Lieshout JJ, Pott F, Madsen PL, van Goudoever J, Secher NH. Muscle tensing during standing: Effects on cerebral tissue oxygenation and cerebral artery blood velocity. Stroke 32: 1546‐1551, 2001.
 665.van Lieshout JJ, Secher NH. Point: Counterpoint: Sympathetic activity does/does not influence cerebral blood flow. Point: Sympathetic activity does influence cerebral blood flow. J Appl Physiol 105: 1364‐1366, 2008.
 666.Van Praag H. Neurogenesis and exercise: Past and future directions. Neuromolecular Med 10: 128‐140, 2008.
 667.VanTeeffelen J, Segal SS. Interaction between sympathetic nerve activation and muscle fibre contraction in resistance vessels of hamster retractor muscle. J Physiol 550: 563‐574, 2003.
 668.VanTeeffelen J, Segal SS. Rapid dilation of arterioles with single contraction of hamster skeletal muscle. Am J Physiol Heart Circ Physiol 290: H119‐H127, 2006.
 669.Vatner SF, Franklin D, Van Citters RL, Braunwald E. Effects of carotid sinus nerve stimulation on blood‐flow distribution in conscious dogs at rest and during exercise. Circ Res 27: 495‐503, 1970.
 670.Vatner SF, Knight DR, Hintze TH. Norepinephrine‐induced beta 1‐adrenergic peripheral vasodilation in conscious dogs. Am J Physiol 249: 49‐56, 1985.
 671.Victor RG, Bertocci LA, Pryor SL, Nunnally RL. Sympathetic nerve discharge is coupled to muscle cell pH during exercise in humans. J Clin Invest 82: 1301‐1305, 1988.
 672.Victor RG, Pryor SL, Secher NH, Mitchell JH. Effects of partial neuromuscular blockade on sympathetic nerve responses to static exercise in humans. Circ Res 65: 468‐476, 1989.
 673.Victor RG, Seals DR, Mark AL. Differential control of heart rate and sympathetic nerve activity during dynamic exercise. Insight from intraneural recordings in humans. J Clin Invest 79: 508‐516, 1987.
 674.Victor RG, Secher NH, Lyson T, Mitchell JH. Central command increases muscle sympathetic nerve activity during intense intermittent isometric exercise in humans. Circ Res 76: 127‐131., 1995.
 675.Vissing SF, Scherrer U, Victor RG. Stimulation of skin sympathetic nerve discharge by central command. Differential control of sympathetic outflow to skin and skeletal muscle during static exercise. Circ Res 69: 228‐238, 1991.
 676.Volianitis S, Yoshiga C, Vogelsang T, Secher N. Arterial blood pressure and carotid baroreflex function during arm and combined arm and leg exercise in humans. Acta Physiol Scand 181: 289‐295, 2004.
 677.Volkers L, Mecihoukhi Y, Coste B. Piezo channels: From structure to function. Pflugers Archiv 467: 95‐99, 2015.
 678.Waaler BA, Toska K, Eriksen M. Involvement of the human splanchnic circulation in pressor response induced by handgrip contraction. Acta Physiol Scand 166: 131‐136, 1999.
 679.Wahlestedt C, Yanaihara N, Hakanson R. Evidence for different pre‐and post‐junctional receptors for neuropeptide Y and related peptides. Regul Pept 13: 307‐318, 1986.
 680.Waldrop T, Bauer R, Iwamoto G. Microinjection of GABA antagonists into the posterior hypothalamus elicits locomotor activity and cardiorespiratory activation. Brain Res 444: 84‐94, 1988.
 681.Waldrop T, Henderson M, Iwamoto G, Mitchell J. Regional blood flow responses to stimulation of the subthalamic locomotor region. Respir Physiol 64: 93‐102, 1986.
 682.Waldrop TG, Eldridge FL, Iwamoto GA, Mitchell JH. Central neural control of respiration and circulation during exercise. In: Handbook of Physiology Exercise: Regulation and Integration of Multiple Systems. Bethesda: American Physiological Society, 1996, pp. 333‐380.
 683.Waldrop TG, Mitchell JH. Effects of barodenervation on cardiovascular responses to static muscular contraction. Am J Physiol 249: H710‐H714, 1985.
 684.Walgenbach S, Donald D. Cardiopulmonary reflexes and arterial pressure during rest and exercise in dogs. Am J Physiol 244: H362‐H369, 1983.
 685.Walgenbach SC, Donald DE. Inhibition by carotid baroreflex of exercise‐induced increases in arterial pressure. Circ Res 52: 253‐262, 1983.
 686.Walker J, Abboud F, Mark A, Thames M. Interaction of cardiopulmonary and somatic reflexes in humans. J Clin Invest 65: 1491‐1497, 1980.
 687.Wallin BG, Esler M, Dorward P, Eisenhofer G, Ferrier C, Westerman R, Jennings G. Simultaneous measurements of cardiac noradrenaline spillover and sympathetic outflow to skeletal muscle in humans. J Physiol 453: 45‐58, 1992.
 688.Wallin BG, Victor RG, Mark AL. Sympathetic outflow to resting muscles during static handgrip and postcontraction muscle ischemia. Am J Physiol 256: H105‐H110, 1989.
 689.Wang HJ, Li YL, Zhang LB, Zucker IH, Gao L, Zimmerman MC, Wang W. Endogenous reactive oxygen species modulates voltage‐gated sodium channels in dorsal root ganglia of rats. J Appl Physiol 110: 1439‐1447, 2011.
 690.Wang HJ, Wang W, Patel KP, Rozanski GJ, Zucker IH. Spinal cord GABA receptors modulate the exercise pressor reflex in decerebrate rats. Am J Physiol 3005: R42‐R49, 2013.
 691.Wang WZ, Gao L, Wang HJ, Zucker IH, Wang W. Tonic glutamatergic input in the rostral ventrolateral medulla is increased in rats with chronic heart failure. Hypertension 53: 370‐374, 2009.
 692.Wehrwein EA, Orer HS, Barman SM. Overview of the anatomy, physiology, and pharmacology of the autonomic nervous system. Compr Physiol 6: 1239‐1278, 2016.
 693.Wildenthal K, Mierzwiak DS, Skinner NS, Jr., Mitchell JH. Potassium‐induced cardiovascular and ventilatory reflexes from the dog hindlimb. Am J Physiol 215: 542‐548, 1968.
 694.Williams CA, Mudd JG, Lind AR. The forearm blood flow during intermittent handgrip isometric exercise. Circ Research 48(Suppl I): I110‐I117, 1978.
 695.Williams MA, Smith SA, O'Brien DE, Mitchell JH, Garry MG. The group IV afferent neuron expresses multiple receptor alterations in cardiomyopathyic rats: Evidence at the cannabinoid CB1 receptor. J Physiol 586: 835‐845, 2008.
 696.Williamson JW, Fadel PJ, Mitchell JH. New insights into central cardiovascular control during exercise in humans: A central command update. Exp Physiol 91: 51‐58, 2006.
 697.Williamson JW, McColl R, Mathews D. Evidence for central command activation of the human insular cortex during exercise. J Appl Physiol 94: 1726‐1734., 2003.
 698.Williamson JW, McColl R, Mathews D, Mitchell JH, Raven PB, Morgan WP. Brain activation by central command during actual and imagined handgrip under hypnosis. J Appl Physiol 92: 1317‐1324, 2002.
 699.Williamson JW, McColl R, Mathews D, Mitchell JH, Raven PB, Morgan WP. Hypnotic manipulation of effort sense during dynamic exercise: Cardiovascular responses and brain activation. J Appl Physiol 90: 1392‐1399, 2001.
 700.Williamson JW, Mitchell JH, Olesen HL, Raven PB, Secher NH. Reflex increase in blood pressure induced by leg compression in man. J Physiol 475: 351‐357, 1994.
 701.Williamson JW, Nobrega AC, Winchester PK, Zim S, Mitchell JH. Instantaneous heart rate increase with dynamic exercise: Central command and muscle‐heart reflex contributions. J Appl Physiol 78: 1273‐1279, 1995.
 702.Wilson JR, Kapoor S. Contribution of endothelium‐derived relaxing factor to exercise‐induced vasodilation in humans. J Appl Physiol 75: 2740‐2744, 1993.
 703.Wilson LB. Spinal modulation of the muscle pressor reflex by nitric oxide and acetycholine. Brain Res Bull 53: 51‐58, 2000.
 704.Wilson LB, Engbretson J, Crews AD. Pressor reflex evoked by static muscle contraction: Role of nitric oxide in the dorsal horn. Am J Physiol 276: R1639‐R1646, 1999.
 705.Wilson LB, Fuchs IE, Matsukawa K, Mitchell JH, Wall PT. Substance P release in the spinal cord during the exercise pressor reflex in anaesthetized cats. J Physiol 460: 79‐90, 1993.
 706.Wilson LB, Wall PT, Matsukawa K, Mitchell JH. Effect of spinal microinjections of an antagonist to substance P or somatostatin on the exercise pressor reflex. Circ Res 70: 213‐222, 1992.
 707.Wingo JE, Low DA, Keller DM, Davis SL, Kowalske KJ, Purdue GF, Hunt JL, Crandall CG. Heat acclimation of an adult female with a large surface area of grafted skin. J Burn Care Res 29: 848‐851, 2008.
 708.Wong BJ, Hollowed CG. Current concepts of active vasodilation in human skin. Temperature 3: 1‐19, 2016.
 709.Wray DW, Fadel PJ, Smith ML, Raven P, Sander M. Inhibition of alpha‐adrenergic vasoconstriction in exercising human thigh muscles. J Physiol 555: 545‐563, 2004.
 710.Wray DW, Nishiyama SK, Donato AJ, Sander M, Wagner PD, Richardson RS. Endothelin‐1‐mediated vasoconstriction at rest and during dynamic exercise in healthy humans. Am J Physiol Heart Circ Physiol 293: H2550‐H2556, 2007.
 711.Yasui Y, Breder CD, Saper CB, Cechetto DF. Autonomic responses and efferent pathways from the insular cortex in the rat. J Comp Neur 303: 355‐374, 1991.
 712.Yen JC, Chan JY, Chan SH. Differential roles of NMDA and non‐NMDA receptors in synaptic responses of neurons in nucleus tractus solitarii of the rat. J Neurophysiol 81: 3034‐3043, 1999.
 713.Zanutto BS, Valentinuzzi ME, Segura ET. Neural set point for the control of arterial pressure: Role of the nucleus tractus solitarius. Biomed Eng Online 9: 4, 2010.
 714.Zhang J, Mifflin SW. Differential roles for NMDA and non‐NMDA receptor subtypes in baroreceptor afferent integration in the nucleus of the solitary tract of the rat. J Physiol 511(Pt 3): 733‐745, 1998.
 715.Zhang J, Mifflin SW. Receptor subtype specific effects of GABA agonists on neurons receiving aortic depressor nerve inputs within the nucleus of the solitary tract. J Auton Nerv Syst 73: 170‐181, 1998.
 716.Zheng H, Li YF, Cornish KG, Zucker IH, Patel KP. Exercise training improves endogenous nitric oxide mechanisms within the paraventricular nucleus in rats with heart failure. Am J Physiol Heart Circ Physiol 288: H2332‐H2341, 2005.
 717.Zucker IH. Novel mechanisms of sympathetic regulation in chronic heart failure. Hypertension 48: 1005‐1011, 2006.
 718.Zucker IH, Patel KP, Schultz HD, Li Y‐F, Wang W, Pliquett RU. Exercise training and sympathetic regulation in experimental heart failure. Exerc Sport Sci Rev 32: 107‐111, 2004.
 719.Zuntz N, Geppert J. Ueber die natur der normalen atemreize und den ort ihrer wirkung. Arch Gen Physiol 38: 337‐338, 1886.

 

Teaching Material

P. J. Mueller, P. S. Clifford, C. G. Crandall, S. A. Smith, P. J. Fadel. Integration of Central and Peripheral Regulation of the Circulation during Exercise: Acute and Chronic Adaptations. Compr Physiol. 8: 2018, 103-151.

Didactic Synopsis

Major Teaching Points:

This article presents specific topics related to control of the cardiovascular system during exercise intended for graduate or advanced undergraduate students:

  • During exercise, increased oxygen demand of contracting muscle is matched by increases in blood flow coordinated by central and peripheral nervous systems.
  • Central command activates neural pathways that initiate movement and the cardiovascular and respiratory pathways to support increased oxygen requirements of exercise.
  • After exercise starts, the brain uses peripheral sensory mechanisms to maintain appropriate oxygen delivery: (i) exercise pressor reflex (detects changes in muscle activity and subsequent byproducts); (ii) arterial baroreflex (detects changes in blood pressure); and (iii) cardiopulmonary reflex (detects changes in central blood volume).
  • Repeated bouts of exercise over time are associated with altered neural pathways (neuroplasticity), influencing the cardiovascular system both at rest and during exercise.
  • Inactivity- and exercise-related neuroplasticity may predispose sedentary individuals to higher incidences of cardiovascular disease and physically active individuals to improved cardiovascular health.

Didactic Legends

The figures—in a freely downloadable PowerPoint format—can be found on the Images tab along with the formal legends published in the article. The following legends to the same figures are written to be useful for teaching.

Figure 1. This figure illustrates two points:

(1) There is an increase in sympathetic nerve activity during exercise compared to rest.

(2) There is a progressive increase in sympathetic nerve activity with increasing exercise intensity.

Figure 2. This schematic presents the key neural mechanisms responsible for mediating the exercise intensity-dependent modulation of the autonomic nervous system (i.e., sympathetic and parasympathetic nerve activity) that occurs during exercise. These autonomic adjustments lead to cardiac and vascular changes that modulate blood pressure and facilitate the increases in blood flow needed to support exercising muscle.

Figure 3. The findings presented from this study demonstrate that passive stretch of the triceps surae muscle in healthy humans evokes increases in heart rate without effecting blood pressure. These date suggest that mechanically sensitive muscle afferents of the exercise pressor reflex may contribute to the increase in heart rate in response to muscle contraction.

Figure 4. These findings show that inhibition of mechano-gated Piezo channels reduced the blood pressure (BP), heart rate (HR), and renal sympathetic nerve activity (RSNA) responses to tendon stretch in decerebrate rats indicating a role for these channels in evoking the cardiovascular responses to activation of the mechanically sensitive muscle afferents of the exercise pressor reflex.

Figure 5. This schematic shows the intensity-dependent resetting of the carotid baroreflex during dynamic exercise from rest to heavy exercise, which allows the baroreflex to maintain control of blood pressure throughout a given bout of exercise.

Figure 6. This figure demonstrates evidence of Central Command in which the brain is capable of initiating movement and changes in blood flow to support the increases in metabolism associated with movement (i.e., muscle contraction). In this example from Williamson and colleagues (698), individuals who were not as easily hypnotized did not have an increase in brain activation (A, left) or increase in heart rate (A, right) during imagined exercise compared to real exercise. In contrast, individuals that could be more easily hypnotized, reported greater perceived effort, similar brain activation (B, left), and increases in heart rate (B, right) during imagined exercise compared to real exercise. Thus, the brain can increase heart rate when it perceives it is performing exercise even when muscular work is not actually being performed. These experiments in particular suggest that the insular and anterior cingulate cortexes play key roles in the brain's control of the cardiovascular system during exercise.

Figure 7. This conceptual framework depicts potential interactions within the central nervous system that allow for the resetting of the arterial baroreflex function curve during exercise to permit a maintained baroreflex control in the face of exercise-induced elevations in blood pressure (BP), heart rate (HR), and sympathetic nerve activity (SNA).

Figure 8. This schematic diagram shows:

(1) There are postsynaptic alpha1 and alpha2 adrenergic, beta2 adrenergic, P2X, and NPY Y1 receptors on the smooth muscle of arterioles in skeletal muscle.

(2) There are postsynaptic muscarinic and P2Y receptors on the endothelial lining of arterioles in skeletal muscle.

(3) Sympathetic signaling to the vasculature can be interrupted by blocking binding of the neurotransmitter to its postsynaptic receptor.

Figure 9. Vascular conductance is a measure of global vessel diameter that accounts for changes in arterial pressure. This figure shows that the initial vasodilation in skeletal muscle during dynamic exercise is independent of the autonomic nervous system.

Figure 10. This figure compares the effect of administering a selective blocker of alpha1 adrenergic receptors, prazosin, to one hindlimb of an exercising dog with the other hindlimb, which received no treatment. The immediate increase in blood flow and vascular conductance in the experimental limb demonstrates that there is tonic activation of alpha1 adrenergic receptors during exercise.

Figure 11. This schematic illustration shows the divergent responses that occur in contracting and inactive skeletal muscle vasculature to increases in muscle sympathetic nerve activity during exercise. The increases in sympathetic outflow are evoked, in large part, via mechanically and metabolically sensitive muscle afferents (the Exercise Pressor Reflex) with further modulation provided by the arterial baroreflex. These intensity-dependent increases in sympathetic nerve activity cause sympathetically mediated vasoconstriction in inactive muscle, whereas in active muscle there is an attenuation of this sympathetic vasoconstrictor activity. This attenuation of sympathetic vasoconstriction in the contracting muscle has been termed functional sympatholysis, which allows for enhanced muscle blood flow to the metabolically active skeletal muscle. At the same time, the sympathetically mediated vasoconstriction in inactive muscle (and the viscera—not pictured) enhances the redistribution of cardiac output to the contracting skeletal muscles.

Figure 12. An illustration of how the brain controls two separate systems that modulate skin blood flow, along with the chemical transmitters known to contribute to those responses. During cooling, skin blood flow decreases due to activation of the vasoconstrictor system. During heating, skin blood flow increases due to activation of the vasodilator system. The chemical transmitters are as follows: NE, norepinephrine; NPY, neuropeptide Y; Ach, acetylcholine; VIP, vasoactive intestinal peptide; PACAP, pituitary adenylate cyclase-activating peptide; nNO, neuronally derived nitric oxide. Illustration used by permission from Manabu Shibasaki, PhD, Nara Women's University.

Figure 13. An illustration of the relationship between internal temperature (esophageal temperature) and the elevation in skin blood flow (expressed as cutaneous vascular conductance), during passive heat stress (rest—closed circles) and exercise-induced heat stress (open circles). These finding show that the increase in skin blood flow during exercise-induced heat stress is delayed relative to passive-induced heat stress. Figure modified from Kellogg, Johnson, and Kosiba, 1991 (280) with permission.

Figure 14. An illustration of the relationship between increases in cardiac output (Q) and corresponding changes in forearm blood flow (FBF—panel A) and brain blood flow (MCAVmean—panel B) in resting and exercising subjects. These data suggest that increases in cardiac output contribute to increases in forearm blood flow and brain blood flow during rest and exercise. Reprinted with permission from Ogoh et al., 2005 (465).

Figure 15. An illustration of the relationship between splanchnic blood flow on the Y-axis and oxygen utilization, expressed in absolute units (VO2) and relative to maximum oxygen utilization (% Max VO2) in diseased patients (MS), in nonfit subjects (Sed), and in trained athletes (Ath) on splanchnic blood flow. These data demonstrate that as a workload becomes more difficult (i.e., requires more oxygen), there are linear reductions in splanchnic blood flow. Reprinted with permission from Rowell, 1973 (533).

Figure 16. Conceptual diagram of the spectrum of physical activity and proposed influence of positive and negative brain effects on cardiovascular health.

Figure 17. Schematic diagram illustrating the role of important neural pathways involved in integration and generation of sympathetic vasoconstrictor outflow.

Figure 18. Schematic diagram illustrating the role of important neural pathways involved in the integration and generation of sympathetic and parasympathetic outflow to the heart.

 


Related Articles:

Neural Control of the Circulation: How Sex and Age Differences Interact in Humans
Cardiovascular Reflex Control by Afferent Fibers from Skeletal Muscle Receptors
Autonomic Adjustments to Exercise in Humans
Overview of the Anatomy, Physiology, and Pharmacology of the Autonomic Nervous System
Neural Control of Vascular Function in Skeletal Muscle

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Integration of Central and Peripheral Regulation of the Circulation during Exercise: Acute and Chronic Adaptations
 

How to Cite

Patrick J. Mueller, Philip S. Clifford, Craig G. Crandall, Scott A. Smith, Paul J. Fadel . Integration of Central and Peripheral Regulation of the Circulation during Exercise: Acute and Chronic Adaptations. Compr Physiol 2017, 8: 103-151. doi: 10.1002/cphy.c160040