Central hemodynamics during incremental exercise to exhaustion. Left column: cardiac output, heart rate (HR), stroke volume, mean arterial (•) and central venous (▾) pressures, and systemic vascular conductance. Right column: arterial O₂ content, systemic O₂ delivery, systemic a‐vO₂ difference, systemic O₂ extraction, and systemic O₂ uptake during incremental exercise to exhaustion plotted against the relative increase in power output. Data are means ± SEM for eight subjects. ^* Lower than 80% of peak power, P < 0.05. Adapted from 951 with permission of the Physiological Society and Wiley‐Blackwell.

Regional distribution of cardiac output during various intensities of exercise expressed as % maximal oxygen consumption. Bar graphs on the left illustrate total cardiac output (sum of all tissue flows) and the regional distribution of cardiac output to all tissues with increasing exercise intensity. Bar graphs on the right show an expansion of regional blood flow (BF) data to all tissues except skeletal muscle tissue, to enhance appreciation of the changes in BF to the other tissue with exercise (Note the change in the BF axis for the graphs on the right). Data are estimated for human values using Rowell's text book 1172 (also estimates for humans) and our data for regional BF in pigs 29,30,239.

Schematic drawing of an arteriole (top) and of endothelium, VSM and parenchymal cell (at the bottom) illustrating mechanisms for control of vasomotor tone and diameter. Adapted from Figure 14 of 295 with permission of the American Physiological Society. Neurohumoral, endothelial, and metabolic influences are detailed in the bottom part of the figure. Abbreviations: K_Ca, calcium‐activated K⁺ channel; K_ATP, ATP‐sensitive K⁺ channel; K_v, voltage‐gated K⁺ channel; K_IR, inward rectifying K⁺ channel; Trp, transient receptor potential channels; O₂, oxygen; ATP, adenosine triphosphate; NO, nitric oxide; TXA₂, thromboxane A₂ and receptor; 5HT, 5‐hydroxytryptamine and receptor; P2, purinergic type 2 receptor; M, muscarinic receptor; H₁ and H₂, histamine type 1 and 2 receptors; B₂, bradykinin type 2 receptor; ECE, endothelin‐converting enzyme; bET‐1, big endothelin‐1; ET‐1, endothelin‐1; eNOS, endothelial nitric oxide synthase; L‐arg, L‐arginine; COX‐1, cyclooxygenase 1; CYP450, cytochrome P450; ACE, angiotensin‐converting enzyme; AI, angiotensin I; AII; angiotensin II; AT₁, angiotensin type 1 receptor; AT₂, angiotensin type 2 receptor; ET_A, endothelin type A receptor; ET_B, endothelin type B receptor; PG, prostaglandins; AA, arachidonic acid; EDHF, endothelium‐derived hyperpolarizing factor; O₂⁻, superoxide anion; VGCC, voltage‐gated calcium channels; IP, prostacyclin receptor; EETs, epoxyeicosatrienoic acids; HETEs, hydroxyeicosatetraenoic acids; H₂O₂, hydrogen peroxide; α₁, α₁‐adrenergic receptor; α₂, α₂‐adrenergic receptor; β₂, β₂‐adrenergic receptor; ACh, acetylcholine; NE, norepinephrine; NPY, neuropeptide Y; P1, purinergic type 1 receptor; and Y₁, neuropeptide Y receptor.

Segmental distribution of control mechanisms throughout the arterial microcirculation, redrawn from 227 with permission of the American Physiological Society.

Relationships between cardiac output (solid symbols) and two‐legged blood flow (open symbols), systemic vascular conductance (solid symbols) and two‐legged vascular conductance (open symbols), and systemic O₂ delivery (solid symbols) and two‐legged O₂ delivery (open symbols) versus the increases in systemic oxygen consumption during incremental exercise to exhaustion. Data are means ± SEM for six subjects. Adapted from 951 with permission of the Physiological Society and Wiley‐Blackwell.

Vasodilation of arterioles and increases in blood flow (BF) can be detected within 1 s after contraction and BF increases with a similar time course in humans. (A) A record of arteriolar diameter and tissue pO2 during single fiber stimulation showing rapid dilation and decrease in pO2. Adapted from 422 with permission of the American Physiological Society. (B) Muscle BF response to a mild‐intensity dynamic exercise bout as measured in dogs with ultrasonic flow probes. Note the immediate increase in BF at the inititation of dynamic exercise (at the arrow). Adapted from 189 with permission of the American Physiological Society. (C) Representative diameter records in 2A branch arterioles after single contractions for durations of 400 and 600 ms of hamster retractor muscle. Adapted from 1409 with permission of the American Physiological Society. (D) Arteriolar dilation following a 250 ms tetanic contraction of 3 to 5 fibers of hamster cremaster muscle. Graphed from data from 915. (E) Femoral artery BF in transition from rest to passive exercise and to voluntary, one‐legged, dynamic knee‐extensor exercise at 10 W (n = 7, 30 W (n = 7, 50 W (n = 5, and 70 W (n = 2. Voluntary exercise started at 0 time. BF was significantly greater than resting BF during passive exercise and during all time points during voluntary exercise and from passive to voluntary exercise. Adapted from Rådegran and Saltin 1121 with permission of the American Physiological Society. (F) Femoral artery BF velocity (V_mean) in transition from rest to passive exercise and to voluntary, one‐legged, dynamic knee‐extensor exercise at 50 W. Knee‐extensor force (F), intramuscular pressure (IMP), arterial (BP_a) and venous (BP_v) blood pressure and HR in beats per minute (BPM) are presented. Onset of voluntary exercise is indicated by an arrow on the tracing for all parameters in panel F. Adapted from Rådegran and Saltin 1121 with permission of the American Physiological Society.

Results of immunoblot analysis of eNOS expression throughout arteriolar trees (each branch order) of gastrocnemius and soleus muscles of rats chronically endurance trained (ET; panels A,C,D) or chronically trained with an interval sprint training program (IST; panel B). Panels A and B present results for the gastrocnemius muscle and panel C presents eNOS expression for the soleus muscle. Panel D presents results for expression of superoxide dismutase (SOD) in feed arteries and arterioles of the soleus muscle. To clarify effects of training, results are expressed relative to protein content of arteries from sedentary rats (SED) as ET/SED or IST/SED. GFA = gastrocnemius feed artery, the first branch from the feed artery is the 1A arteriole and the branches of the 1A are subsequent 2A branches etc. WG = white portion of the gastrocnemius muscle and RG = the red portion of the gastrocnemius muscle. SFA is the soleus feed artery and the branches of the arterioles in the soleus are S1A, S2A, etc. Note that ET resulted in significant increases in eNOS protein in the arterioles feeding red muscle while IST training exhibited increased eNOS in the GFA, and WG4A and RG5A arterioles. Endurance training did not alter eNOS or SOD‐1 expression in the soleus arterioles. Endurance trained results are from McAllister et al. 883 and those for the IST rats are from Laughlin et al. 779. * = value different from 1.0 with p < 0.05; + = value different from 1.0 with p < 0.1.

Distribution of total CO among legs, respiratory muscles (RM), and other metabolically active tissues (skin, heart, brain, kidneys, and liver) during exercise at o₂ max. Adapted from 489 with permission of the American Physiological Society.

Bar graphs of calf blood flow at rest and during maximal hyperemia (post ischemic exercise) in sedentary and trained younger and older women (top panel) and men (bottom panel). Maximal hyperemia was elicited by ischemic exercise to fatigue and measuring flow after release of the occlusion. Data are mean ±SD. ^*P < 0.01, ^**P < 0.05 versus younger subjects of corresponding gender and training status. †P < 0. 01, ‡P < 0.05 versus sedentary subjects of corresponding age and gender

. § P < 0.01, §§ P < 0.05 versus men of similar age and training status. Data taken, with permission, from Martin et al. 868.

Arm blood flow (ABF) and a‐vO₂ difference during arm cranking to exhaustion in rowers and average, fit subjects. A + L, addition of leg exercise to arm cranking in the rowers. Values are means ± SE for eight average fit subjects and seven rowers. Adapted from Volianitis et al. 1429 with permission of the American Physiological Society.

Upper limb (arm) and lower limb (leg) muscle blood flow (BF) (top) and vascular conductance (bottom) from rest to peak exercise. Submaximal (SM) exercise was expressed in terms of relative exercise intensity, SM1, SM2, and SM3 (approx. 40%, 60%, and 80%, of peak power respectively). Values are mean ± SEM. ^*; significantly different from controls. §; significantly different from swimmers. Irrespective of the group, BF max and conductance was increased significantly from rest to peak exercise. Adapted from Walther et al. 1447 with permission of Acta Physiologica.

Changes in arteriolar density do not explain changes in blood flow (BF) capacity following interval sprint training (IST) and endurance exercise training (ET). Results illustrate the effects of training on oxidative capacity (cytochrome c concentrations), BF capacity, capillary density, and arteriolar density in rat skeletal muscles. All data are expressed as a % increase above respective SED values. The IST training consisted of 10 weeks of 6 training bouts/day, 5 days/week, with each rat running 60 m/min up a 15% incline for 2.5 min with 4.5 min of rest between bouts. The ET training program consisted of 10 to 12 weeks of treadmill running at 30 m/min, 60 min/day, 5 days/week. The top row of data are for the white portion of the gastrocnemius muscle (G_W), the middle row for the red portion of the gastrocnemius muscle (G_R), and the bottom row of data are for the soleus muscle. These data indicate that IST increased oxidative capacity and BF capacity most in the G_W muscle and these changes were correlated with increases in capillary density and small increases in arteriolar density. In contrast, ET increased oxidative capacity and BF capacity most in the soleus and G_R muscle but these changes were not correlated with changes in capillary or arteriolar density in the soleus muscle. In the G_R muscle, ET increases in BF capacity were similar to increases in arteriolar density. Of interest, IST increased oxidative capacity and BF capacity in the G_R muscle but neither capillary nor arteriolar density were altered in this muscle tissue by IST. These data were taken from 289,457,458,759,767,774.

Leg blood flow responses to graded upright cycle ergometer in younger and older healthy adults. Most results indicate that the hyperemic response to large muscle dynamic exercise is blunted in older humans. Adapted from Proctor and Parker 1106 with permission of the Microcirculatory Society.

Myocardial oxygen balance in awake dogs at rest and during four incremental levels of treadmill exercise. The increase in myocardial oxygen consumption was principally accounted for by an increase in coronary blood flow with only modest contributions of increase in hematocrit and oxygen extraction. MVO₂, myocardial oxygen consumption, Hct, hematocrit, ArtSO₂, arterial oxygen saturation, CVSO₂, coronary venous oxygen saturation. Data are from von Restorff et al. 1431, and have been presented as mean ± SE. ^*P < 0.05 versus rest. Modified from 295 with permission of the American Physiological Society.

Relations between HR and left ventricular myocardial blood flow (LVMBF) at rest and during treadmill exercise in dogs 45,46,47,51,52,56,64,68,271,294,297,298,301,354,429,431,593,786,803,987,1050,1061,1148,1258,12591258, 1259, 13911391, 13921392, 1394,1431,1512, swine 134,135,296,303,304,474,764,1004,1005,1205,1206,1308,1309,1337,1467 and horses 31,858,862,1070. Data from humans were obtained principally from young healthy male subjects performing upright bicycle exercise 324,511,546,622,623,685,727,979,980,986,1140,1454,1492,14931492, 1493). Data from rats 285,286,373 have been added (solid circles) to illustrate that the high LVMBF values in this species are the result of the high heart rates, so that the rat data fall close to the regression line for the human data. Modified from 295 with permission of the American Physiological Society.

Relation between Mo₂ and coronary venous oxygen tension (left panel) and oxygen saturation (right panel) at rest and during treadmill exercise in humans 511, swine 296, horses 859,1070, and dogs 45,1431. Note that exercise does not alter coronary venous oxygen tension in swine, whereas it is already reduced at low levels of exercise in dogs. Humans and horses demonstrate an intermediate oxygen tension response. During exercise oxygen saturation decreases in horses and humans (similar to dogs) whereas in swine saturation is not affected, suggesting a rightward shift of the hemoglobin‐oxygen dissociation curve during exercise in humans and horses. Also note that despite similar resting coronary venous oxygen tensions, horses and humans have higher hemoglobin‐oxygen saturations as compared to swine and dogs, consistent with the higher P₅₀ values reported in the latter species 585,1151. Data are mean ± SE. ^*P < 0.05 versus corresponding rest. See text for further explanation. Modified from 295 with permission of the American Physiological Society.

Coronary blood flow and hemodynamic responses to treadmill exercise in dogs. Modified from Khouri et al. 672. L. Circ. = left circumflex coronary artery; Cor. = coronary; Syst. = systolic; Diast. = diastolic. See text for further explanation. Modified from 295 with permission of the American Physiological Society.

Coronary pressure‐flow relation in the dog heart under conditions of maximal coronary vasodilation with intracoronary adenosine (50 μg/kg/min). Shown are the relations at rest and during three incremental levels of treadmill exercise. Note the rightward shift of the pressure‐flow relation with an increase in the zero flow pressure (Pzf) intercept. See text for further explanation. Data are from Duncker et al. 308 and have been presented as mean ± SE. ^*P < 0.05 versus corresponding rest. Modified from 295 with permission of the American Physiological Society.

Graph showing a schematic drawing of the intramyocardial microvasculature (upper panel) and the extravascular forces acting on the coronary microvasculature during diastole (left lower panel) and systole (lower right panel). Abbreviations: P_IM = intramyocardial pressure; P_LUMEN = pressure in left ventricular lumen; P_PERI = pressure in pericardial space; P_PERI = pressure in pericardial space; Left ventricular lumen pressure. See text for further explanation. Modified from 295 with permission of the American Physiological Society.

Distribution of left ventricular myocardial blood flow in the dog at rest (open symbols) and during exercise (solid symbols) in the presence of intact vasomotor tone (circles) and during maximum vasodilation with intracoronary adenosine (squares). Data are from Duncker et al. 297 and have been presented as mean ± SE. ^*P < 0.05 versus corresponding rest. Dot inside symbol denotes significant (P < 0.05) increase in flow produced by adenosine. Modified from 295 with permission of the American Physiological Society.

Relation between heart rate (HR) and left ventricular subendocardial to subepicardial blood flow (BF) ratio (LV ENDO/EPI) at rest and during treadmill exercise in dogs 45,47,52,271,297,987,1050, swine 134,135,304,474,719,758,1004,10051004, 1005, 12051205, 12061206) and horses 31,858,1070, measured with microspheres 15 μm in diameter. No data on transmural distribution of left ventricular BF are available in humans. Note that exercise results in a modest decrease in ENDO/EPI ratio, but this typically does not decrease below 1.0 even during heavy exercise. Also note that ENDO/EPI ratios are lower and decrease more during exercise in horses (LV E/E = −1.37•HR + 1.30) than in either swine (LV E/E = −1.17•HR + 1.38) or dogs (LV E/E = −1.06•HR + 1.41). Modified from 295 with permission of the American Physiological Society.

Relation beween myocardial oxygen consumption (MVO₂) and coronary venous oxygen tension (CVPO₂) in the right ventricle (RV) and the left ventricle (LV) in dogs during treadmill exercise. Note the lower levels of MVO₂ and higher levels of CVPO₂ in the RV compared to the LV. Data are from Hart et al. 496 for RV data and from Gorman et al. 431 for LV data. Data have been presented as mean ± SE. See text for further explanation. Modified from 295 with permission of the American Physiological Society.

Left panels show the effect of mixed α₁‐/α₂‐adrenergic receptor blockade with phentolamine on the relation between myocardial oxygen consumption (MVO₂) and coronary venous oxygen tension (CVPO₂) in the left ventricles of dogs 48 and swine 305 during treadmill exercise. Right panels show the effect of combined α₁‐/α₂ and β₁‐/β₂‐adrenergic receptor blockade with phentolamine and propranolol in swine 305 and dogs 431. Data are mean ± SE. ^*P < 0.05 versus corresponding control or versuscorresponding phentolamine alone. See text for further explanation. Modified from 295 with permission of the American Physiological Society.

Integrative metabolic control of coronary vasomotor tone in dogs (left panels) and swine (right panels) at rest and during treadmill exercise. Shown are the effects of adenosine receptor blockade with 8‐phenyltheophylline [8PT 5 mg/kg iv 49,906; upper panels], the effects of K_ATP channel blockade with glibenclamide [Glib; 50 μg/kg/min ic 307,309, or 3 mg/kg iv 906] and additional adenosine receptor blockade (middle panels), and the effects of NO synthase inhibition with N‐nitro‐L‐arginine [LNA, 1.5 mg/kg ic 592 or 20 mg/kg iv 906] and additional adenosine receptor blockade and K_ATP channel blockade (lower panels) on the relation between myocardial oxygen consumption (Mo₂) and coronary venous oxygen tension (CVPO₂) in the left ventricles. Data in dogs are from references 49,309,592. Swine data are from Merkus et al. 906. Data are mean ± SEM. ^*P < 0.05 effect of 8PT; ^†P < 0.05 effect of glibenclamide; ^‡P < 0.05 effect of LNA. See text for further explanation. Modified from 295 with permission of the American Physiological Society.

Effects of exercise training in swine on DNA labeling in capillaries (top left panel), sprouting of new capillaries (top middle panel), % labeling of sprouts (top right panel), capillary diameter (bottom left panel), capillary density (bottom middle panel), and coronary transport reserve (CTR; bottom right panel). Data are from White et al. 1465 and have been presented as mean ± SE. ^*P < 0.05 versus 0 week time point (sedentary swine). See text for further explanation. Modified from 295 with permission of the American Physiological Society.

Graph summarizing the structural and functional coronary microcirculatory adaptations to chronic exercise training. ACh = acetylcholine; M = muscarinic receptor; NE = norepinephrine; α₁ = α₁‐adrenergic receptor. β₂ = β₂‐adrenergic receptor. Modified from 295 with permission of the American Physiological Society.

Indices of cerebral blood flow (BF) and oxygenation during progressive exercise expressed as % of baseline value. Arterial carbon dioxide tension (Paco₂). Frontal lobe oxygenation (Sco₂) determined with near‐infrared spectroscopy. The calculated average cerebral mitochondrial oxygen tension (P_mitoO₂). The cerebral oxygen consumption rate (CMRO₂). Middle cerebral artery mean flow velocity (MCA V_mean). Cerebral BF expressed as grey matter flow (F₁) and as the average flow (ISI) during cycling exercise. ISI and F₁ were not determined during maximal exercise. Data from 420,573,626,627,1252,1363.

Linear relationships between middle cerebral artery mean flow velocity (MCA V_mean) and cardiac output () at rest and during exercise. • Rest ○ Exercise. Data are means (SEM). Modified from 1026 with permission of the Physiological Society and Wiley‐Blackwell.

Effects of leg muscle tensing on arterial pressure oscillations and low‐frequency power spectrum. Left: original recording. Middle: beat‐to‐beat values. Right: fast Fourier power spectrum of mean arterial pressure. The amplitude of the oscillations in arterial pressure during standing (upper panel) is attenuated during leg tensing (lower panel) with a reduction in the low‐frequency (0.07 to 0.15 Hz) power spectrum. Modified from, with permission, the Ph.D. Thesis of Pott, 2003 (1096, 1097).

Regional cerebral blood flow (rCBF) by ¹³³Xe SPECT at rest and during static handgrip exercise before and after regional blockade in 1 subject. Scale (right) represents absolute flow values. There is an increase in flow to the motor sensory area in control contraction condition (upper right) compared with rest or with contractions after axillary blockade. Premotor rCBF increased from 55 44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63 to 60 50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69 ml/100 g/liter/min (n = 8 and motor sensor rCBF from 57 46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65 to 63 55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71 ml/liter/100 g/liter/min to both the ipsilateral and contralateral sides during handgrip exercise before, but not after, axillary blockade. Modified from Friedman et al. 392 with permission of the American Physiological Society.

Schematic description of the thermoregulatory control of skin blood flow (BF) as modified by moderately intense exercise. The relation of skin BF to internal temperature is affected, relative to resting conditions, in at least three ways by exercise: a vasoconstrictor response at the onset of dynamic exercise (A), an increase in the internal temperature threshold at which skin BF begins to increase (B), and a leveling off, or plateau, in skin BF above an internal temperature of 38°C at a level well below maximal (C). Exercise exerts these effects through the vasoconstrictor system for the initial vasoconstriction and through inhibiting the active vasodilator system for the increased threshold and for the plateau. At rest, the plateau only occurs as skin BF approaches maximal vasodilation. Modified from Gonzalez‐Alonso et al. 2008 419 with permission of the Physiological Society and Wiley‐Blackwell.

Heterogeneity of blood flow (BF) to various bone tissue in anesthetized dogs. Values below the bars reflect the number of observations for the mean value illustrated. Epiphysis is from the femur inferior epiphysis; “diaphysis represents 28 samples of femur diaphysis and 8 samples of humerus diaphysis.” BFs from the two diaphyseal regions were not significantly different (P > 0.05; “red marrow” is from the femur medulla, and “yellow marrow” represents samples from the medullas of the tibia and mandible. Analysis of variance and Tukey's test indicate the following significant differences: sternum, rib, ilium, and epiphysis > diaphysis and yellow marrow; sternum > rib; red and yellow marrow > diaphysis; red marrow > yellow marrow. Modified from Gross et al. 1979 454 with permission of the American Physiological Society.

Relationship between splanchnic blood flow (BF) and exercise intensity (expressed as percent o₂ max) at normal temperature (25.6°C, solid line) and during heat stress (43.3°C, dashed line). The reduction of splanchnic BF during exercise is proportional to the relative exercise intensity (%o₂ max) and is further reduced by environmental heat stress resulting in ∼20% greater reductions in splanchnic BF at a given relative exercise intensity. Modified from Rowell, 1993 1177 which was adapted from Rowell 1965 1180 with permission of the American Physiological Society.

Exercise‐induced reductions in both splanchnic blood flow (BF) and splanchnic blood volume are nonuniformly distributed across the splanchnic organs. (A) Nonuniform changes in splanchnic BF during and 2 minutes after termination of cycling. The decreases in total splanchnic BF (SBF) (top panel) during moderate cycling exercise involve greater reductions in celiac artery BF (dotted line; middle panel) than in the superior mesenteric artery BF (solid line; middle panel) owing to differential increases in artery resistance (R) in the celiac (dotted line) and superior mesenteric artery (solid line) vascular beds (bottom panel). For both BF and R data in the middle and bottom panels, respectively; continuous line = superior mesenteric artery and the dashed line = the celiac artery. * = different from the preceding value, P < 0.05; # = different from rest, P < 0.05. Data from Perko et al. 1079 with permission of the American Physiological Society. (B) Nonuniform changes in splanchnic blood volume. Splanchnic blood volume redistribution during zero‐load (ZLC) and graded cycling exercise (50%‐100% maximal exercise) and 5 min of recovery from exercise. Note that the volume redistribution involves a greater reduction of splenic than hepatic and renal blood volume and that bowel blood volume did not significantly change from baseline values during or following exercise. Values are % basal volume, mean ± SE. Data taken from Table 3 of Flamm et al. 1990 374.

Exercise training alters the redistribution of blood flow (BF) to kidney and splanchnic tissues during exercise. Top panel: baseline/resting BF values represent sedentary rats standing quietly on the treadmill. Middle panel: exercise BF values for sedentary rats at 15 min of treadmill running 30 m/min. Bottom panel: exercise BF values for exercise trained rats at 15 min of treadmill running 30 m/min. Baseline BFs were similar between sedentary and trained rats. As shown in the middle panel, exercise caused BF reductions to all organs, except the liver in sedentary animals. In contrast, results presented in the bottom panel indicate that trained animals exhibit an attenuated reduction of splanchnic and renal BFs during acute exercise. Values are mean ± SE. Liver BF represents hepatic artery BF only. Data are from Armstrong and Laughlin 33 and McAllister 882.

Graded cycling exercise markedly increases renal vascular resistance thereby reducing renal blood flow (inferred from reduced renal venous outflow). Workloads were 30%, 60%, and 80% to 90% o₂ max. Values are mean ± SE. The *, **, and *** indicate values significantly different from rest, with p < 0.05, 0.01, and 0.001, respectively. Adapted from Tidgren et al. 1370 with permission of the American Physiological Society

.

Changes in pulmonary artery pressure (PAP, open circles in left panels), left atrial pressure (solid circles in left panels) and pulmonary vascular resistance (PVR, right panels) as a function of estimated exercise intensity in dogs 327, swine 1323, sheep 701, humans 1139, and horses 860. Note that PVR is inversely related to body weight (dogs ∼15 kg; swine and sheep ∼25 kg; humans ∼75 kg; and horses ∼400 kg). Exercise intensity is calculated based on heart rate (dogs, sheep, and horses) and/or body oxygen consumption (swine and humans). From Merkus et al. 904 with permission of Elsevier.

Integrated endothelial control of pulmonary vascular tone in swine (554). The vasodilator effect of ET_A/ET_B receptor blockade with tezosentan was enhanced by prior inhibition of eNOS (middle panels), but not by COX inhibition (bottom panels) at rest and during exercise in swine. These findings indicate that NO limits the influence of ET on the pulmonary vasculature. Bo₂: body oxygen consumption; PAP: pulmonary artery pressure; PVR: pulmonary vascular resistance. ^*P < 0.05 versus control, †P < 0.05 effect of tezosentan different after eNOS/COX inhibition. Adapted from Merkus et al. 904 with permission of Elsevier.

Autonomic control of pulmonary vascular tone in swine 1323. α‐Adrenoceptor blockade results in vasodilation (top), whereas β‐adrenoceptor blockade results in vasoconstriction at rest and during exercise (middle). Hence, the sympathetic nervous system exerts no net effect on pulmonary vascular tone. M‐receptor blockade results in pulmonary vasodilation at rest that wanes with increasing exercise intensity (bottom), suggesting that withdrawal of the vasoconstrictor influence exerted by the parasympathetic nervous system contributes to exercise‐induced pulmonary vasodilation. Bo₂: body oxygen consumption; PAP: pulmonary artery pressure; PVR: pulmonary vascular resistance. ^*P < 0.05 versus control. From Merkus et al. 904 1323 with permission of Elsevier.

Schematic regulation of the pulmonary vascular tone at rest and during exercise in the healthy pulmonary circulation. NO: nitric oxide; PGI₂: prostacyclin; β_AR: β adrenoceptor; M_R: muscarinic receptor; Ado: adenosine; ANP: atrial natriuretic peptide; K_ATP, K_Ca²⁺ and K_V: ATP, Ca²⁺ and voltage‐sensitive K‐channels; ET_A: endothelin A receptor; ET_B: endothelin B receptor; α_AR: α‐adrenoceptor; Ang‐II: angiotensin II; TXA₂: thromboxane A₂; 5‐HT: 5‐hydroxytryptamine; PDE5: phosphodiesterase 5; ROS: reactive oxygen species; +: significant influence; −: no influence; ?: probable influence (not yet proven). See text for further explanations. From Merkus et al. 904 with permission of Elsevier.