Autonomic Cardiovascular Control in Health and Disease

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Autonomic Cardiovascular Control in Health and Disease

Shahid Karim, Anwar Chahal, Mohammed Y. Khanji, Steffen E. Petersen, Virend K. Somers

10.1002/cphy.c210037

Source: Volume 13, Issue 2, April 2023

Published online: March 2023

Full Article on Wiley Online Library

Abstract
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References

Abstract

Autonomic neural control of the cardiovascular system is formed of complex and dynamic processes able to adjust rapidly to mitigate perturbations in hemodynamics and maintain homeostasis. Alterations in autonomic control feature in the development or progression of a multitude of diseases with wide‐ranging physiological implications given the neural system's responsibility for controlling inotropy, chronotropy, lusitropy, and dromotropy. Imbalances in sympathetic and parasympathetic neural control are also implicated in the development of arrhythmia in several cardiovascular conditions sparking interest in autonomic modulation as a form of treatment.

A number of measures of autonomic function have shown prognostic significance in health and in pathological states and have undergone varying degrees of refinement, yet adoption into clinical practice remains extremely limited. The focus of this contemporary narrative review is to summarize the anatomy, physiology, and pathophysiology of the cardiovascular autonomic nervous system and describe the merits and shortfalls of testing modalities available. © 2023 American Physiological Society. Compr Physiol 13:4493‐4511, 2023.

	Figure 1. A broad timeline of major discoveries of the autonomic nervous system. Claude Bernard – Claude Bernard/Wikimedia Commons/Public Domain; Walter Bradford Cannon – Desconocido/Wikimedia Commons/CC BY 4.0; Henry Hallett Dale – Michieli/Wikimedia Commons/CC BY 4.0; James Black – M.M. Mee/Wikimedia Commons/CC BY 4.0; John Newport Langley – John Newport Langley/Wellcome Collection/CC BY 4.0; Otto Loewi – Otto Loewi/Wellcome Collection/CC BY 4.0; Raymond Ahlquist – Raymond Ahlquist/U.S. National Library of Medicine/Public Domain.
	Figure 2. Autonomic afferent nerve scheme of the baroreceptors governing blood pressure. Used with permission of Mayo Foundation for Medical Education and Research, all rights reserved.
	Figure 3. Pathway of catecholamine synthesis.
	Figure 4. Catecholamine metabolism.
	Figure 5. Cardiac autonomic nervous system. Used with permission of Mayo Foundation for Medical Education and Research, all rights reserved.
	Figure 6. Sympathetic and parasympathetic innervation of the heart and splanchnic arterial bed. Used with permission of Mayo Foundation for Medical Education and Research, all rights reserved.
	Figure 7. Modified Oxford baroreflex test. ECG, RR interval, and blood pressure recordings following sodium nitroprusside (NP) and phenylephrine (PHE) bolus injections. Blood pressure fall is followed by a rise in response to the bolus injections. Reproduced with permission 21.
	Figure 8. Arterial pressure and heart rate response to the Valsalva maneuver. The four described phases of the baroreflex are indicated on the graphs. Reproduced with permission 82.
	Figure 9. Characteristics of sudomotor autonomic failure in multiple system atrophy. (A) Preserved postganglionic sweat responses [Quantitative Sudomotor Axon Reflex Test (QSART)] with complete anhidrosis on the Thermoregulatory Sweat Test (TST), suggesting a central or preganglionic lesion. (B) Rapid progression (from 0% to 66% body surface anhidrosis) in only 1 year (sweating in shaded areas). Reproduced with permission 69.

Figure 1. A broad timeline of major discoveries of the autonomic nervous system. Claude Bernard – Claude Bernard/Wikimedia Commons/Public Domain; Walter Bradford Cannon – Desconocido/Wikimedia Commons/CC BY 4.0; Henry Hallett Dale – Michieli/Wikimedia Commons/CC BY 4.0; James Black – M.M. Mee/Wikimedia Commons/CC BY 4.0; John Newport Langley – John Newport Langley/Wellcome Collection/CC BY 4.0; Otto Loewi – Otto Loewi/Wellcome Collection/CC BY 4.0; Raymond Ahlquist – Raymond Ahlquist/U.S. National Library of Medicine/Public Domain.

Figure 3. Pathway of catecholamine synthesis.

Figure 4. Catecholamine metabolism.

Figure 7. Modified Oxford baroreflex test. ECG, RR interval, and blood pressure recordings following sodium nitroprusside (NP) and phenylephrine (PHE) bolus injections. Blood pressure fall is followed by a rise in response to the bolus injections. Reproduced with permission 21.

Figure 8. Arterial pressure and heart rate response to the Valsalva maneuver. The four described phases of the baroreflex are indicated on the graphs. Reproduced with permission 82.

Figure 9. Characteristics of sudomotor autonomic failure in multiple system atrophy. (A) Preserved postganglionic sweat responses [Quantitative Sudomotor Axon Reflex Test (QSART)] with complete anhidrosis on the Thermoregulatory Sweat Test (TST), suggesting a central or preganglionic lesion. (B) Rapid progression (from 0% to 66% body surface anhidrosis) in only 1 year (sweating in shaded areas). Reproduced with permission 69.

References
1.	Accurso V, Winnicki M, Shamsuzzaman AS, Wenzel A, Johnson AK, Somers VK. Predisposition to vasovagal syncope in subjects with blood/injury phobia. Circulation 104: 903‐907, 2001.
2.	Ackerman MJ, Tester DJ, Porter CJ. Swimming, a gene‐specific arrhythmogenic trigger for inherited long QT syndrome. Mayo Clin Proc 74: 1088‐1094, 1999.
3.	Ahlquist RP. A study of the adrenotropic receptors. Am J Physiol 153: 586‐600, 1948.
4.	Akselrod S, Gordon D, Ubel FA, Shannon DC, Berger AC, Cohen RJ. Power spectrum analysis of heart rate fluctuation: A quantitative probe of beat‐to‐beat cardiovascular control. Science 213: 220‐222, 1981.
5.	Angell‐James JE, Daly MB. Some aspects of upper respiratory tract reflexes. Acta Otolaryngol 79: 242‐252, 1975.
6.	Antony I, Aptecar E, Lerebours G, Nitenberg A. Coronary artery constriction caused by the cold pressor test in human hypertension. Hypertension 24: 212‐219, 1994.
7.	Asmussen E, Kristiansson NG. The “diving bradycardia” in exercising man. Acta Physiol Scand 73: 527‐535, 1968.
8.	Aubert AE, Seps B, Beckers F. Heart rate variability in athletes. Sports Med 33: 889‐919, 2003.
9.	Aviado DM, Guevara AD. The Bezold‐Jarisch reflex. A historical perspective of cardiopulmonary reflexes. Ann N Y Acad Sci 940: 48‐58, 2001.
10.	Bainbridge FA. The influence of venous filling upon the rate of the heart. J Physiol 50: 65‐84, 1915.
11.	Bandler R, Keay KA, Floyd N, Price J. Central circuits mediating patterned autonomic activity during active vs. passive emotional coping. Brain Res Bull 53: 95‐104, 2000.
12.	Becker DE. Basic and clinical pharmacology of autonomic drugs. Anesth Prog 59: 159‐168; quiz 169, 2012.
13.	Becker HF, Jerrentrup A, Ploch T, Grote L, Penzel T, Sullivan CE, Peter JH. Effect of nasal continuous positive airway pressure treatment on blood pressure in patients with obstructive sleep apnea. Circulation 107: 68‐73, 2003.
14.	Benarroch EE. The arterial baroreflex: Functional organization and involvement in neurologic disease. Neurology 71: 1733‐1738, 2008.
15.	Bertinieri G, Di Rienzo M, Cavallazzi A, Ferrari AU, Pedotti A, Mancia G. Evaluation of baroreceptor reflex by blood pressure monitoring in unanesthetized cats. Am J Phys 254: H377‐H383, 1988.
16.	Bettoni M, Zimmermann M. Autonomic tone variations before the onset of paroxysmal atrial fibrillation. Circulation 105: 2753‐2759, 2002.
17.	Biaggioni I, Onrot J, Stewart CK, Robertson D. The potent pressor effect of phenylpropanolamine in patients with autonomic impairment. JAMA 258: 236‐239, 1987.
18.	Biscoe TJ, Purves MJ, Sampson SR. The frequency of nerve impulses in single carotid body chemoreceptor afferent fibres recorded in vivo with intact circulation. J Physiol 208: 121‐131, 1970.
19.	Black JW. Ahlquist and the development of beta‐adrenoceptor antagonists. Postgrad Med J 52 (Suppl 4): 11‐13, 1976.
20.	Bond V, Curry BH, Adams RG, Obisesan T, Pemminati S, Gorantla VR, Kadur K, Millis RM. Cardiovascular responses to an isometric handgrip exercise in females with prehypertension. N Am J Med Sci 8: 243‐249, 2016.
21.	Bonyhay I, Risk M, Freeman R. High‐pass filter characteristics of the baroreflex ‐ A comparison of frequency domain and pharmacological methods. PLoS One 8: e79513, 2013.
22.	Brush JE Jr, Eisenhofer G, Garty M, Stull R, Maron BJ, Cannon RO 3rd, Panza JA, Epstein SE, Goldstein DS. Cardiac norepinephrine kinetics in hypertrophic cardiomyopathy. Circulation 79: 836‐844, 1989.
23.	Buccelletti F, Gilardi E, Scaini E, Galiuto L, Persiani R, Biondi A, Basile F, Gentiloni SN. Heart rate variability and myocardial infarction: Systematic literature review and metanalysis. Eur Rev Med Pharmacol Sci 13: 299‐307, 2009.
24.	Burke WJ, Li SW, Chung HD, Ruggiero DA, Kristal BS, Johnson EM, Lampe P, Kumar VB, Franko M, Williams EA, Zahm DS. Neurotoxicity of MAO metabolites of catecholamine neurotransmitters: Role in neurodegenerative diseases. Neurotoxicology 25: 101‐115, 2004.
25.	Burnstock G. Autonomic neurotransmission: 60 Years since Sir Henry Dale. Annu Rev Pharmacol Toxicol 49: 1‐30, 2009.
26.	Butler PJ, Jones DR. Physiology of diving of birds and mammals. Physiol Rev 77: 837‐899, 1997.
27.	Cao JM, Fishbein MC, Han JB, Lai WW, Lai AC, Wu TJ, Czer L, Wolf PL, Denton TA, Shintaku IP, Chen PS, Chen LS. Relationship between regional cardiac hyperinnervation and ventricular arrhythmia. Circulation 101: 1960‐1969, 2000.
28.	Carter JR, Goldstein DS. Sympathoneural and adrenomedullary responses to mental stress. Compr Physiol 5: 119‐146, 2015.
29.	Charkoudian N, Wallin BG. Sympathetic neural activity to the cardiovascular system: Integrator of systemic physiology and interindividual characteristics. Compr Physiol 4: 825‐850, 2014.
30.	Chida Y, Steptoe A. Greater cardiovascular responses to laboratory mental stress are associated with poor subsequent cardiovascular risk status: A meta‐analysis of prospective evidence. Hypertension 55: 1026, 2010‐1032.
31.	Cohn JN, Levine TB, Olivari MT, Garberg V, Lura D, Francis GS, Simon AB, Rector T. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med 311: 819‐823, 1984.
32.	Convertino VA, Ratliff DA, Doerr DF, Ludwig DA, Muniz GW, Benedetti E, Chavarria J, Koreen S, Nguyen C, Wang J. Effects of repeated Valsalva maneuver straining on cardiac and vasoconstrictive baroreflex responses. Aviat Space Environ Med 74: 212‐219, 2003.
33.	Cordero DR, Brugmann S, Chu Y, Bajpai R, Jame M, Helms JA. Cranial neural crest cells on the move: Their roles in craniofacial development. Am J Med Genet A 155a: 270‐279, 2011.
34.	Dae MW, O'Connell JW, Botvinick EH, Ahearn T, Yee E, Huberty JP, Mori H, Chin MC, Hattner RS, Herre JM, et al. Scintigraphic assessment of regional cardiac adrenergic innervation. Circulation 79: 634‐644, 1989.
35.	Daly MB, Ungar A. Comparison of the reflex responses elicited by stimulation of the separately perfused carotid and aortic body chemoreceptors in the dog. J Physiol 182: 379‐403, 1966.
36.	Dampney RA, Horiuchi J. Functional organisation of central cardiovascular pathways: Studies using c‐fos gene expression. Prog Neurobiol 71: 359‐384, 2003.
37.	Dampney RA, Horiuchi J, Killinger S, Sheriff MJ, Tan PS, McDowall LM. Long‐term regulation of arterial blood pressure by hypothalamic nuclei: Some critical questions. Clin Exp Pharmacol Physiol 32: 419‐425, 2005.
38.	Davies L, Francis D, Jurak P, Kara T, Piepoli M, Coats A. Reproducibility of methods for assessing baroreflex sensitivity in normal controls and in patients with chronic heart failure. Clin Sci 97: 515‐522, 1999.
39.	Davis RW, Polasek L, Watson R, Fuson A, Williams TM, Kanatous SB. The diving paradox: New insights into the role of the dive response in air‐breathing vertebrates. Comp Biochem Physiol A Mol Integr Physiol 138: 263‐268, 2004.
40.	De BC. I'influence de syst'eme nerveaux grand sympathetique sur la chaleur animal. C R Acad Sci 34: 472‐475, 1852.
41.	Deuchars SA, Lall VK. Sympathetic preganglionic neurons: Properties and inputs. Compr Physiol 5: 829‐869, 2015.
42.	Dimitrow PP, Krzanowski M, Nitankowski R, Szczeklik A, Dubiel JS. The effect of verapamil on response of coronary vasomotion to handgrip exercise in symptomatic patients with hypertrophic cardiomyopathy. Cardiovasc Drugs Ther 15: 331‐337, 2001.
43.	Dimitrow PP, Krzanowski M, Nizankowski R, Szczeklik A, Dubiel JS. Verapamil improves the response of coronary vasomotion to cold pressor test in asymptomatic and mildly symptomatic patients with hypertrophic cardiomyopathy. Cardiovasc Drugs Ther 13: 259‐264, 1999.
44.	Dolezel S. Monoaminergic innervation of the kidney. Aorticorenal ganglion ‐ A sympathetic, monoaminergic ganglion supplying the renal vessels. Experientia 23: 109‐111, 1967.
45.	Dudenbostel T, Calhoun DA. Resistant hypertension, obstructive sleep apnoea and aldosterone. J Hum Hypertens 26: 281‐287, 2012.
46.	Eckberg DL. Point:counterpoint: Respiratory sinus arrhythmia is due to a central mechanism vs. respiratory sinus arrhythmia is due to the baroreflex mechanism. J Appl Physiol (1985) 106: 1740‐1742; discussion 1744, 2009.
47.	Eckberg DL, Cavanaugh MS, Mark AL, Abboud FM. A simplified neck suction device for activation of carotid baroreceptors. J Lab Clin Med 85: 167‐173, 1975.
48.	ESC/NASPE. Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation 93: 1043‐1065, 1996.
49.	Esler M, Jackman G, Bobik A, Kelleher D, Jennings G, Leonard P, Skews H, Korner P. Determination of norepinephrine apparent release rate and clearance in humans. Life Sci 25: 1461‐1470, 1979.
50.	Esler M, Jennings G, Lambert G, Meredith I, Horne M, Eisenhofer G. Overflow of catecholamine neurotransmitters to the circulation: Source, fate, and functions. Physiol Rev 70: 963‐985, 1990.
51.	Ewing DJ, Clarke BF. Diagnosis and management of diabetic autonomic neuropathy. Br Med J (Clin Res Ed) 285: 916‐918, 1982.
52.	Fukuda K, Kanazawa H, Aizawa Y, Ardell JL, Shivkumar K. Cardiac innervation and sudden cardiac death. Circ Res 116: 2005‐2019, 2015.
53.	Goldstein DS. Dysautonomia in Parkinson disease. Comp. Phys. 4 (2): 805‐826, 2014.
54.	Goldstein DS. Concepts of scientific integrative medicine applied to the physiology and pathophysiology of catecholamine systems. Compr Physiol 3: 1569‐1610, 2013.
55.	Gordon FJ, Leone C. Non‐NMDA receptors in the nucleus of the tractus solitarius play the predominant role in mediating aortic baroreceptor reflexes. Brain Res 568: 319‐322, 1991.
56.	Graham DG. Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones. Mol Pharmacol 14: 633‐643, 1978.
57.	Guo YP, McLeod JG, Baverstock J. Pathological changes in the vagus nerve in diabetes and chronic alcoholism. J Neurol Neurosurg Psychiatry 50: 1449‐1453, 1987.
58.	Guyenet PG. Regulation of breathing and autonomic outflows by chemoreceptors. Compr Physiol 4: 1511‐1562, 2014.
59.	Halámek J, Kára T, Jurák P, Souček M, Francis DP, Davies LC, Shen WK, Coats AJS, Novák M, Nováková Z, Panovský R, Toman J, Šumbera J, Somers VK. Variability of phase shift between blood pressure and heart rate fluctuations. Circulation 108: 292‐297, 2003.
60.	Harvey W. Exercitatio anatomica de motucordis et sanguinis in animalibus. Springfield, Illinois: Charles C. Thomas Publishing, 1628.
61.	Herring N, Paterson DJ, Paterson DJ, and Levick JR. Levick's Introduction to Cardiovascular Physiology. Florida, USA: CRC Press, 2018.
62.	Hilz MJ, Axelrod FB, Braeske K, Stemper B. Cold pressor test demonstrates residual sympathetic cardiovascular activation in familial dysautonomia. J Neurol Sci 196: 81‐89, 2002.
63.	Hislop HJ. The autonomic nervous system: Morphological, comparative, clinical and surgical aspects. Phys Ther 52: 119‐120, 1972.
64.	Horsman HM, Peebles KC, Galletly DC, Tzeng YC. Cardiac baroreflex gain is frequency dependent: Insights from repeated sit‐to‐stand maneuvers and the modified Oxford method. Appl Physiol Nutr Metab 38: 753‐759, 2013.
65.	Hull SS Jr, Vanoli E, Adamson PB, Verrier RL, Foreman RD, Schwartz PJ. Exercise training confers anticipatory protection from sudden death during acute myocardial ischemia. Circulation 89: 548‐552, 1994.
66.	Imadojemu VA, Mawji Z, Kunselman A, Gray KS, Hogeman CS, Leuenberger UA. Sympathetic chemoreflex responses in obstructive sleep apnea and effects of continuous positive airway pressure therapy. Chest 131: 1406‐1413, 2007.
67.	Imrich R, Eldadah BA, Bentho O, Pechnik S, Sharabi Y, Holmes C, Goldstein DS. Attenuated pre‐ejection period response to tyramine in patients with cardiac sympathetic denervation. Ann N Y Acad Sci 1148: 486‐489, 2008.
68.	Inoue H, Zipes DP. Time course of denervation of efferent sympathetic and vagal nerves after occlusion of the coronary artery in the canine heart. Circ Res 62: 1111‐1120, 1988.
69.	Iodice V, Lipp A, Ahlskog JE, Sandroni P, Fealey RD, Parisi JE, Matsumoto JY, Benarroch EE, Kimpinski K, Singer W, Gehrking TL, Gehrking JA, Sletten DM, Schmeichel AM, Bower JH, Gilman S, Figueroa J, Low PA. Autopsy confirmed multiple system atrophy cases: Mayo experience and role of autonomic function tests. J Neurol Neurosurg Psychiatry 83: 453‐459, 2012.
70.	Iturriaga R, Alcayaga J. Neurotransmission in the carotid body: Transmitters and modulators between glomus cells and petrosal ganglion nerve terminals. Brain Res Brain Res Rev 47: 46‐53, 2004.
71.	Jacob G, Ertl AC, Shannon JR, Furlan R, Robertson RM, Robertson D. Effect of standing on neurohumoral responses and plasma volume in healthy subjects. J Appl Physiol 84: 914‐921, 1998.
72.	Janes RD, Brandys JC, Hopkins DA, Johnstone DE, Murphy DA, Armour JA. Anatomy of human extrinsic cardiac nerves and ganglia. Am J Cardiol 57: 299‐309, 1986.
73.	Jänig W. Sympathetic nervous system and inflammation: A conceptual view. Auton Neurosci 182: 4‐14, 2014.
74.	Jarisch ARH. Die kreislauf des veratrins. Arch Exp Pathol Pharmacol 193: 347‐354, 1939.
75.	Kalia M. Brain stem localization of vagal preganglionic neurons. J Auton Nerv Syst 3: 451‐481, 1981.
76.	Kamarck TW, Lovallo WR. Cardiovascular reactivity to psychological challenge: Conceptual and measurement considerations. Psychosom Med 65: 9‐21, 2003.
77.	Kara T, Narkiewicz K, Somers VK. Chemoreflexes ‐ Physiology and clinical implications. Acta Physiol Scand 177: 377‐384, 2003.
78.	Kawada T, Yamazaki T, Akiyama T, Shishido T, Miyano H, Sato T, Sugimachi M, Alexander J Jr, Sunagawa K. Interstitial norepinephrine level by cardiac microdialysis correlates with ventricular contractility. Am J Phys 273: H1107‐H1112, 1997.
79.	Kennedy B, Shen GH, Ziegler MG. Neuropeptide Y‐mediated pressor responses following high‐frequency stimulation of the rat sympathetic nervous system. J Pharmacol Exp Ther 281: 291‐296, 1997.
80.	Kirby ML, Gilmore SA. A correlative histofluorescence and light microscopic study of the formation of the sympathetic trunks in chick embryos. Anat Rec 186: 437‐449, 1976.
81.	Kline DD. Chronic intermittent hypoxia affects integration of sensory input by neurons in the nucleus tractus solitarii. Respir Physiol Neurobiol 174: 29‐36, 2010.
82.	Kosinski SA, Carlson BE, Hummel SL, Brook RD, Beard DA. Computational model‐based assessment of baroreflex function from response to Valsalva maneuver. J Appl Physiol (1985) 125: 1944‐1967, 2018.
83.	Krassioukov AV, Bygrave MA, Puckett WR, Bunge RP, Rogers KA. Human sympathetic preganglionic neurons and motoneurons retrogradely labelled with DiI. J Auton Nerv Syst 70: 123‐128, 1998.
84.	Kristensson K, Nordborg C, Olsson Y, Sourander P. Changes in the vagus nerve in diabetes mellitus. Acta Pathol Microbiol Scand A 79: 684‐685, 1971.
85.	Kumar P, Prabhakar NR. Peripheral chemoreceptors: Function and plasticity of the carotid body. Compr Physiol 2: 141‐219, 2012.
86.	La Rovere MT, Bigger JT Jr, Marcus FI, Mortara A, Schwartz PJ. Baroreflex sensitivity and heart‐rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) Investigators. Lancet 351: 478‐484, 1998.
87.	Langley JN. On the union of cranial autonomic (visceral) fibres with the nerve cells of the superior cervical ganglion. J Physiol 23: 240‐270, 1898.
88.	Lavoie JL, Sigmund CD. Minireview: Overview of the renin‐angiotensin system ‐ An endocrine and paracrine system. Endocrinology 144: 2179‐2183, 2003.
89.	Le Douarin NM, Creuzet S, Couly G, Dupin E. Neural crest cell plasticity and its limits. Development 131: 4637‐4650, 2004.
90.	LeDoux J. The amygdala. Curr Biol 17: R868‐R874, 2007.
91.	Lefroy DC, de Silva R, Choudhury L, Uren NG, Crake T, Rhodes CG, Lammertsma AA, Boyd H, Patsalos PN, Nihoyannopoulos P, et al. Diffuse reduction of myocardial beta‐adrenoceptors in hypertrophic cardiomyopathy: A study with positron emission tomography. J Am Coll Cardiol 22: 1653‐1660, 1993.
92.	Leuenberger UA, Hardy JC, Herr MD, Gray KS, Sinoway LI. Hypoxia augments apnea‐induced peripheral vasoconstriction in humans. J Appl Physiol (1985) 90: 1516‐1522, 2001.
93.	Li K, Lindauer C, Haase R, Rüdiger H, Reichmann H, Reuner U, Ziemssen T. Autonomic dysfunction in Wilson's disease: A comprehensive evaluation during a 3‐year follow up. Front Physiol 8: 778, 2017.
94.	Loewy AD. Anatomy of the autonomic nervous system: An overview. In: Arthur D. Loewy and K. Michael Spyer, editors. Central Regulation of Autonomic Functions. Oxford University Press, 1990, p. 3‐17.
95.	Lombardi F, Porta A, Marzegalli M, Favale S, Santini M, Vincenti A, De Rosa A. Heart rate variability patterns before ventricular tachycardia onset in patients with an implantable cardioverter defibrillator. Participating Investigators of ICD‐HRV Italian Study Group. Am J Cardiol 86: 959‐963, 2000.
96.	Maehle AH. “Receptive substances”: John Newport Langley (1852‐1925) and his path to a receptor theory of drug action. Med Hist 48: 153‐174, 2004.
97.	Maheshwari A, Norby FL, Soliman EZ, Adabag S, Whitsel EA, Alonso A, Chen LY. Low heart rate variability in a 2‐minute electrocardiogram recording is associated with an increased risk of sudden cardiac death in the general population: The atherosclerosis risk in communities study. PLoS One 11: e0161648, 2016.
98.	Malliani A, Pagani M, Lombardi F, Cerutti S. Cardiovascular neural regulation explored in the frequency domain. Circulation 84: 482‐492, 1991.
99.	Mancia G, Ferrari A, Gregorini L, Parati G, Pomidossi G, Bertinieri G, Grassi G, Zanchetti A. Blood pressure variability in man: Its relation to high blood pressure, age and baroreflex sensitivity. Clin Sci (Lond) 59 (Suppl 6): 401s‐404s, 1980.
100.	Manousiouthakis E, Mendez M, Garner MC, Exertier P, Makita T. Venous endothelin guides sympathetic innervation of the developing mouse heart. Nat Commun 5: 3918, 2014.
101.	Mark AL. The Bezold‐Jarisch reflex revisited: Clinical implications of inhibitory reflexes originating in the heart. J Am Coll Cardiol 1: 90‐102, 1983.
102.	Martins JB, Kerber RE, Marcus ML, Laughlin DL, Levy DM. Inhibition of adrenergic neurotransmission in ischaemic regions of the canine left ventricle. Cardiovasc Res 14: 116‐124, 1980.
103.	Maser RE, Mitchell BD, Vinik AI, Freeman R. The association between cardiovascular autonomic neuropathy and mortality in individuals with diabetes: A meta‐analysis. Diabetes Care 26: 1895‐1901, 2003.
104.	McCorry LK. Physiology of the autonomic nervous system. Am J Pharm Educ 71: 78, 2007.
105.	Milic M, Sun P, Liu F, Fainman C, Dimsdale J, Mills PJ, Ziegler MG. A comparison of pharmacologic and spontaneous baroreflex methods in aging and hypertension. J Hypertens 27: 1243‐1251, 2009.
106.	Montano N, Porta A, Cogliati C, Costantino G, Tobaldini E, Casali KR, Iellamo F. Heart rate variability explored in the frequency domain: A tool to investigate the link between heart and behavior. Neurosci Biobehav Rev 33: 71‐80, 2009.
107.	Narkiewicz K, Somers VK. The sympathetic nervous system and obstructive sleep apnea: Implications for hypertension. J Hypertens 15: 1613‐1619, 1997.
108.	Ng GA, Mantravadi R, Walker WH, Ortin WG, Choi BR, de Groat W, Salama G. Sympathetic nerve stimulation produces spatial heterogeneities of action potential restitution. Heart Rhythm 6: 696‐706, 2009.
109.	Niskanen JP, Tarvainen MP, Ranta‐Aho PO, Karjalainen PA. Software for advanced HRV analysis. Comput Methods Prog Biomed 76: 73‐81, 2004.
110.	Nurse CA. Neurotransmission and neuromodulation in the chemosensory carotid body. Auton Neurosci 120: 1‐9, 2005.
111.	O'Brien IA, O'Hare JP, Lewin IG, Corrall RJ. The prevalence of autonomic neuropathy in insulin‐dependent diabetes mellitus: A controlled study based on heart rate variability. QJM 61: 957‐967, 1986.
112.	O'Connell TD, Swigart PM, Rodrigo MC, Ishizaka S, Joho S, Turnbull L, Tecott LH, Baker AJ, Foster E, Grossman W, Simpson PC. Alpha1‐adrenergic receptors prevent a maladaptive cardiac response to pressure overload. J Clin Invest 116: 1005‐1015, 2006.
113.	Oosting J, Struijker‐Boudier HA, Janssen BJ. Validation of a continuous baroreceptor reflex sensitivity index calculated from spontaneous fluctuations of blood pressure and pulse interval in rats. J Hypertens 15: 391‐399, 1997.
114.	Pagani M, Somers V, Furlan R, Dell'Orto S, Conway J, Baselli G, Cerutti S, Sleight P, Malliani A. Changes in autonomic regulation induced by physical training in mild hypertension. Hypertension 12: 600‐610, 1988.
115.	Palma JA, Benarroch EE. Neural control of the heart: Recent concepts and clinical correlations. Neurology 83: 261‐271, 2014.
116.	Parati G, Mutti E, Frattola A, Castiglioni P, di Rienzo M, Mancia G. Beta‐adrenergic blocking treatment and 24‐hour baroreflex sensitivity in essential hypertensive patients. Hypertension 23: 992‐996, 1994.
117.	Pardal R, López‐Barneo J. Low glucose‐sensing cells in the carotid body. Nat Neurosci 5: 197‐198, 2002.
118.	Patel MB, Loud AV, King BD, Anversa P, Sack D, Hintze TH. Global myocardial hypertrophy in conscious dogs with chronic elevation of plasma norepinephrine levels. J Mol Cell Cardiol 21 (Suppl 5): 49‐61, 1989.
119.	Paton JF, Nalivaiko E, Boscan P, Pickering AE. Reflexly evoked coactivation of cardiac vagal and sympathetic motor outflows: Observations and functional implications. Clin Exp Pharmacol Physiol 33: 1245‐1250, 2006.
120.	Peelaerts W, Bousset L, Van der Perren A, Moskalyuk A, Pulizzi R, Giugliano M, Van den Haute C, Melki R, Baekelandt V. α‐Synuclein strains cause distinct synucleinopathies after local and systemic administration. Nature 522: 340‐344, 2015.
121.	Penäz J. Photoelectric measurement of blood pressure, volume and flow in the finger. Digest of the International Conference on Medicine and Biological Engineering, 9, 104 abstract I, 1973.
122.	Pinna GD, Maestri R. New criteria for estimating baroreflex sensitivity using the transfer function method. Med Biol Eng Comput 40: 79‐84, 2002.
123.	Pinna GD, Maestri R, Capomolla S, Febo O, Robbi E, Cobelli F, La Rovere MT. Applicability and clinical relevance of the transfer function method in the assessment of baroreflex sensitivity in heart failure patients. J Am Coll Cardiol 46: 1314‐1321, 2005.
124.	Polinsky RJ, Kopin IJ, Ebert MH, Weise V. Pharmacologic distinction of different orthostatic hypotension syndromes. Neurology 31: 1‐7, 1981.
125.	Pop‐Busui R. Cardiac autonomic neuropathy in diabetes: A clinical preservative. Diabetes Care 33: 434‐441, 2010.
126.	Prabhakar NR, Peng YJ, Kumar GK, Nanduri J. Peripheral chemoreception and arterial pressure responses to intermittent hypoxia. Compr Physiol 5: 561‐577, 2015.
127.	Pruvot E, Thonet G, Vesin JM, van Melle G, Seidl K, Schmidinger H, Brachmann J, Jung W, Hoffmann E, Tavernier R, Block M, Podczeck A, Fromer M. Heart rate dynamics at the onset of ventricular tachyarrhythmias as retrieved from implantable cardioverter‐defibrillators in patients with coronary artery disease. Circulation 101: 2398‐2404, 2000.
128.	Pumprla J, Howorka K, Groves D, Chester M, Nolan J. Functional assessment of heart rate variability: Physiological basis and practical applications. Int J Cardiol 84: 1‐14, 2002.
129.	Robbe HW, Mulder LJ, Rüddel H, Langewitz WA, Veldman JB, Mulder G. Assessment of baroreceptor reflex sensitivity by means of spectral analysis. Hypertension 10: 538‐543, 1987.
130.	Santiago TVEN. Brain blood flow and control of breathing. Compr Physiol: 163‐179, 2011. https://onlinelibrary.wiley.com/doi/abs/10.1002/cphy.cp030206
131.	Saper CB. The central autonomic nervous system: Conscious visceral perception and autonomic pattern generation. Annu Rev Neurosci 25: 433‐469, 2002.
132.	Sassi R, Cerutti S, Lombardi F, Malik M, Huikuri HV, Peng C‐K, Schmidt G, Yamamoto Y, Document Reviewers: Gorenek B, Lip GYH, Grassi G, Kudaiberdieva G, Fisher JP, Zabel M, and Macfadyen RAdvances in heart rate variability signal analysis: Joint position statement by the e‐Cardiology ESC Working Group and the European Heart Rhythm Association co‐endorsed by the Asia Pacific Heart Rhythm Society. EP Europace 17: 1341‐1353, 2015.
133.	Schmidt RE. Neuropathology and pathogenesis of diabetic autonomic neuropathy. Int Rev Neurobiol 50: 257‐292, 2002.
134.	Shaffer F, Ginsberg JP. An overview of heart rate variability metrics and norms. Front Public Health 5: 258, 2017.
135.	Shamsuzzaman A, Ackerman MJ, Kuniyoshi FS, Accurso V, Davison D, Amin RS, Somers VK. Sympathetic nerve activity and simulated diving in healthy humans. Auton Neurosci 181: 74‐78, 2014.
136.	Shen MJ, Zipes DP. Role of the autonomic nervous system in modulating cardiac arrhythmias. Circ Res 114: 1004‐1021, 2014.
137.	Shields RW Jr. Functional anatomy of the autonomic nervous system. J Clin Neurophysiol 10: 2‐13, 1993.
138.	Shoemaker JK, Badrov MB, Al‐Khazraji BK, Jackson DN. Neural control of vascular function in skeletal muscle. Compr Physiol 6: 303‐329, 2015.
139.	Singal PK, Dhillon KS, Beamish RE, Kapur N, Dhalla NS. Myocardial cell damage and cardiovascular changes due to i.v. infusion of adrenochrome in rats. Br J Exp Pathol 63: 167‐176, 1982.
140.	Singer W, Berini SE, Sandroni P, Fealey RD, Coon EA, Suarez MD, Benarroch EE, Low PA. Pure autonomic failure: Predictors of conversion to clinical CNS involvement. Neurology 88: 1129‐1136, 2017.
141.	Somers VK, Conway J, Johnston J, Sleight P. Effects of endurance training on baroreflex sensitivity and blood pressure in borderline hypertension. Lancet 337: 1363‐1368, 1991.
142.	Somers VK, Conway J, LeWinter M, Sleight P. The role of baroreflex sensitivity in post‐exercise hypotension. J Hypertens Suppl 3: S129‐S130, 1985.
143.	Somers VK, Mark AL, Abboud FM. Interaction of baroreceptor and chemoreceptor reflex control of sympathetic nerve activity in normal humans. J Clin Invest 87: 1953‐1957, 1991.
144.	Somers VK, Mark AL, Zavala DC, Abboud FM. Contrasting effects of hypoxia and hypercapnia on ventilation and sympathetic activity in humans. J Appl Physiol (1985) 67: 2101‐2106, 1989.
145.	Somers VK, Mark AL, Zavala DC, Abboud FM. Influence of ventilation and hypocapnia on sympathetic nerve responses to hypoxia in normal humans. J Appl Physiol 67: 2095‐2100, 1989.
146.	Stroop JR. Studies of interference in serial verbal reactions. J Exp Psychol 18: 643‐662, 1935.
147.	Suarez‐Roca H, Mamoun N, Sigurdson MI, Maixner W. Baroreceptor modulation of the cardiovascular system, pain, consciousness, and cognition. Compr Physiol 11: 1373‐1423, 2021.
148.	Tank AW, Lee WD. Peripheral and central effects of circulating catecholamines. Compr Physiol 5: 1‐15, 2015.
149.	Thomas GD. Neural control of the circulation. Adv Physiol Educ 35: 28‐32, 2011.
150.	Tipre DN, Goldstein DS. Cardiac and extracardiac sympathetic denervation in Parkinson's disease with orthostatic hypotension and in pure autonomic failure. J Nucl Med 46: 1775‐1781, 2005.
151.	Trimarco B, Volpe M, Ricciardelli B, Vigorito C, De Luca N, Saccà L, Condorelli M. Valsalva maneuver in the assessment of baroreflex responsiveness in borderline hypertensives. Cardiology 70: 6‐14, 1983.
152.	Vinik AI, Maser RE, Mitchell BD, Freeman R. Diabetic autonomic neuropathy. Diabetes Care 26: 1553‐1579, 2003.
153.	von Bezold AVHL. Uber die physiologischen wirkungen des essigsauren veratrins. In: Gscheidlen R, editor. Untersuchungen aus dem Physiologischen Laboratorium Wurzburg, vol. 1. Nabu Press. 1867, p. 75‐156.
154.	Waxman MB, Asta JA, Cameron DA. Vasodepressor reaction induced by inferior vena cava occlusion and isoproterenol in the rat. Role of beta 1‐ and beta 2‐adrenergic receptors. Circulation 89: 2401‐2411, 1994.
155.	Wehrwein EA, Orer HS, Barman SM. Overview of the anatomy, physiology, and pharmacology of the autonomic nervous system. Compr Physiol 6: 1239‐1278, 2016.
156.	Wesseling KH, Settels JJ, de Wit B. The measurement of continuous finger arterial pressure noninvasively in stationary subjects. In: Schmidt TH, Dembroski TM, Blümchen G, editors. Biological and Psychological Factors in Cardiovascular Disease. Berlin, Heidelberg: Springer Berlin Heidelberg, 1986, p. 355‐375.
157.	Yoshida M, Fukumoto Y, Kuroda Y, Ohkoshi N. Sympathetic denervation of myocardium demonstrated by 123I‐MIBG scintigraphy in pure progressive autonomic failure. Eur Neurol 38: 291‐296, 1997.
158.	Zeng WZ, Marshall KL, Min S, Daou I, Chapleau MW, Abboud FM, Liberles SD, Patapoutian A. PIEZOs mediate neuronal sensing of blood pressure and the baroreceptor reflex. Science 362: 464‐467, 2018.
159.	Zipes DP. Influence of myocardial ischemia and infarction on autonomic innervation of heart. Circulation 82: 1095‐1105, 1990.

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Article Title:	Autonomic Cardiovascular Control in Health and Disease
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Shahid Karim, Anwar Chahal, Mohammed Y. Khanji, Steffen E. Petersen, Virend K. Somers. Autonomic Cardiovascular Control in Health and Disease. Compr Physiol 2023, 13: 4493-4511. doi: 10.1002/cphy.c210037

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