Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

The sympathetic nervous system and blood pressure in humans: implications for hypertension

Journal of Human Hypertension volume 26, pages 463–475 (2012)Cite this article

Abstract

A neurogenic component to primary hypertension (hypertension) is now well established. Along with raised vasomotor tone and increased cardiac output, the chronic activation of the sympathetic nervous system in hypertension has a diverse range of pathophysiological consequences independent of any increase in blood pressure. This review provides a perspective on the actions and interactions of angiotensin II, inflammation and vascular dysfunction/brain hypoperfusion in the pathogenesis and progression of neurogenic hypertension. The optimisation of current treatment strategies and the exciting recent developments in the therapeutic targeting of the sympathetic nervous system to control hypertension (for example, catheter-based renal denervation and carotid baroreceptor stimulation) will be outlined.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Carretero OA, Oparil S . Essential hypertension. Part I: definition and etiology. Circulation 2000; 101 (3): 329–335.

    CAS  PubMed  Google Scholar 

  2. Esler M . The 2009 Carl Ludwig Lecture: pathophysiology of the human sympathetic nervous system in cardiovascular diseases: the transition from mechanisms to medical management. J Appl Physiol 2010; 108 (2): 227–237.

    CAS  PubMed  Google Scholar 

  3. Esler M, Lambert E, Schlaich M . Point: chronic activation of the sympathetic nervous system is the dominant contributor to systemic hypertension. J Appl Physiol 2010; 109 (6): 1996–1998; discussion 2016.

    PubMed  Google Scholar 

  4. Folkow B . Physiological aspects of primary hypertension. Physiol Rev 1982; 62 (2): 347–504.

    CAS  PubMed  Google Scholar 

  5. Navar LG . Counterpoint: activation of the intrarenal renin-angiotensin system is the dominant contributor to systemic hypertension. J Appl Physiol 2010; 109 (6): 1998–2000; discussion 2015.

    PubMed  PubMed Central  Google Scholar 

  6. Anderson EA, Sinkey CA, Lawton WJ, Mark AL . Elevated sympathetic nerve activity in borderline hypertensive humans. Evidence from direct intraneural recordings. Hypertension 1989; 14 (2): 177–183.

    CAS  PubMed  Google Scholar 

  7. Simms AE, Paton JF, Pickering AE, Allen AM . Amplified respiratory-sympathetic coupling in the spontaneously hypertensive rat: does it contribute to hypertension? J Physiol 2009; 587 (Part 3): 597–610.

    CAS  PubMed  Google Scholar 

  8. Smith PA, Graham LN, Mackintosh AF, Stoker JB, Mary DA . Sympathetic neural mechanisms in white-coat hypertension. J Am Coll Cardiol 2002; 40 (1): 126–132.

    PubMed  Google Scholar 

  9. Smith PA, Graham LN, Mackintosh AF, Stoker JB, Mary DA . Relationship between central sympathetic activity and stages of human hypertension. Am J Hypertens 2004; 17 (3): 217–222.

    PubMed  Google Scholar 

  10. Morrissey DM, Brookes VS, Cooke WT . Sympathectomy in the treatment of hypertension; review of 122 cases. Lancet 1953; 1 (6757): 403–408.

    CAS  PubMed  Google Scholar 

  11. Krum H, Sobotka P, Mahfoud F, Bohm M, Esler M, Schlaich M . Device-based antihypertensive therapy: therapeutic modulation of the autonomic nervous system. Circulation 2011; 123 (2): 209–215.

    PubMed  Google Scholar 

  12. Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, Bohm M . Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet 2010; 376 (9756): 1903–1909.

    PubMed  Google Scholar 

  13. Krum H, Schlaich M, Whitbourn R, Sobotka PA, Sadowski J, Bartus K et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet 2009; 373 (9671): 1275–1281.

    PubMed  Google Scholar 

  14. Wustmann K, Kucera JP, Scheffers I, Mohaupt M, Kroon AA, de Leeuw PW et al. Effects of chronic baroreceptor stimulation on the autonomic cardiovascular regulation in patients with drug-resistant arterial hypertension. Hypertension 2009; 54 (3): 530–536.

    CAS  PubMed  Google Scholar 

  15. Fisher JP, Young CN, Fadel PJ . Central sympathetic overactivity: maladies and mechanisms. Auton Neurosci 2009; 148 (1–2): 5–15.

    PubMed  PubMed Central  Google Scholar 

  16. Paton JF, Waki H, Abdala AP, Dickinson J, Kasparov S . Vascular-brain signaling in hypertension: role of angiotensin II and nitric oxide. Curr Hypertens Rep 2007; 9 (3): 242–247.

    CAS  PubMed  Google Scholar 

  17. Peterson JR, Sharma RV, Davisson RL . Reactive oxygen species in the neuropathogenesis of hypertension. Curr Hypertens Rep 2006; 8 (3): 232–241.

    CAS  PubMed  Google Scholar 

  18. Goldstein DS . Plasma catecholamines and essential hypertension. An analytical review. Hypertension 1983; 5 (1): 86–99.

    CAS  PubMed  Google Scholar 

  19. Grassi G, Esler M . How to assess sympathetic activity in humans. J Hypertens 1999; 17 (6): 719–734.

    CAS  PubMed  Google Scholar 

  20. 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 1990; 70 (4): 963–985.

    CAS  PubMed  Google Scholar 

  21. Esler M, Lambert G, Jennings G . Increased regional sympathetic nervous activity in human hypertension: causes and consequences. J Hypertens Suppl 1990; 8 (7): S53–S57.

    CAS  PubMed  Google Scholar 

  22. Vallbo AB, Hagbarth KE, Torebjork HE, Wallin BG . Somatosensory, proprioceptive, and sympathetic activity in human peripheral nerves. Physiol Rev 1979; 59 (4): 919–957.

    CAS  PubMed  Google Scholar 

  23. Esler M, Jennings G, Korner P, Willett I, Dudley F, Hasking G et al. Assessment of human sympathetic nervous system activity from measurements of norepinephrine turnover. Hypertension 1988; 11 (1): 3–20.

    CAS  PubMed  Google Scholar 

  24. Grassi G, Colombo M, Seravalle G, Spaziani D, Mancia G . Dissociation between muscle and skin sympathetic nerve activity in essential hypertension, obesity, and congestive heart failure. Hypertension 1998; 31 (1): 64–67.

    CAS  PubMed  Google Scholar 

  25. Huggett RJ, Burns J, Mackintosh AF, Mary DA . Sympathetic neural activation in nondiabetic metabolic syndrome and its further augmentation by hypertension. Hypertension 2004; 44 (6): 847–852.

    CAS  PubMed  Google Scholar 

  26. Lambert E, Straznicky N, Schlaich M, Esler M, Dawood T, Hotchkin E et al. Differing pattern of sympathoexcitation in normal-weight and obesity-related hypertension. Hypertension 2007; 50 (5): 862–868.

    CAS  PubMed  Google Scholar 

  27. Esler M, Lambert G, Vaz M, Thompson J, Kaye D, Kalff V et al. Central nervous system monoamine neurotransmitter turnover in primary and obesity-related human hypertension. Clin Exp Hypertens 1997; 19 (5–6): 577–590.

    CAS  PubMed  Google Scholar 

  28. Grassi G . Role of the sympathetic nervous system in human hypertension. J Hypertens 1998; 16 (12 Part 2): 1979–1987.

    CAS  PubMed  Google Scholar 

  29. Grassi G, Cattaneo BM, Seravalle G, Lanfranchi A, Mancia G . Baroreflex control of sympathetic nerve activity in essential and secondary hypertension. Hypertension 1998; 31 (1): 68–72.

    CAS  PubMed  Google Scholar 

  30. Joyner MJ, Charkoudian N, Wallin BG . A sympathetic view of the sympathetic nervous system and human blood pressure regulation. Exp Physiol 2008; 93 (6): 715–724.

    PubMed  PubMed Central  Google Scholar 

  31. Singh JP, Larson MG, Tsuji H, Evans JC, O’Donnell CJ, Levy D . Reduced heart rate variability and new-onset hypertension: insights into pathogenesis of hypertension: the Framingham Heart Study. Hypertension 1998; 32 (2): 293–297.

    CAS  PubMed  Google Scholar 

  32. Gerritsen J, Dekker JM, TenVoorde BJ, Kostense PJ, Heine RJ, Bouter LM et al. Impaired autonomic function is associated with increased mortality, especially in subjects with diabetes, hypertension, or a history of cardiovascular disease: the Hoorn Study. Diabetes Care 2001; 24 (10): 1793–1798.

    CAS  PubMed  Google Scholar 

  33. Friberg P, Karlsson B, Nordlander M . Sympathetic and parasympathetic influence on blood pressure and heart rate variability in Wistar-Kyoto and spontaneously hypertensive rats. J Hypertens Suppl 1988; 6 (4): S58–S60.

    CAS  PubMed  Google Scholar 

  34. Judy WV, Farrell SK . Arterial baroreceptor reflex control of sympathetic nerve activity in the spontaneously hypertensive rat. Hypertension 1979; 1 (6): 605–614.

    CAS  PubMed  Google Scholar 

  35. Lundin S, Ricksten SE, Thoren P . Renal sympathetic activity in spontaneously hypertensive rats and normotensive controls, as studied by three different methods. Acta Physiol Scand 1984; 120 (2): 265–272.

    CAS  PubMed  Google Scholar 

  36. Cabassi A, Vinci S, Calzolari M, Bruschi G, Borghetti A . Regional sympathetic activity in pre-hypertensive phase of spontaneously hypertensive rats. Life Sci 1998; 62 (12): 1111–1118.

    CAS  PubMed  Google Scholar 

  37. Korner P, Bobik A, Oddie C, Friberg P . Sympathoadrenal system is critical for structural changes in genetic hypertension. Hypertension 1993; 22 (2): 243–252.

    CAS  PubMed  Google Scholar 

  38. Zoccal DB, Paton JF, Machado BH . Do changes in the coupling between respiratory and sympathetic activities contribute to neurogenic hypertension? Clin Exp Pharmacol Physiol 2009; 36 (12): 1188–1196.

    CAS  PubMed  Google Scholar 

  39. Fisher JP, McIntyre D, Farquhar WB, Pickering AE, Lip GYH, Paton JFR . Influence of respiratory phase on muscle sympathetic nerve activity in human hypertension. FASEB J 2011; 25: 1076.2.

    Google Scholar 

  40. Fisher JP, Reynolds RF, Farquhar WB, Pickering AE, Lip GYH, Paton JFR . Respiratory modulation of muscle sympathetic nerve activity in patients with hypertension. Proc Physiol Soc 2010; 20: PC28.

    Google Scholar 

  41. 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 1989; 21 (Suppl 5): 49–61.

    CAS  PubMed  Google Scholar 

  42. Burns J, Sivananthan MU, Ball SG, Mackintosh AF, Mary DA, Greenwood JP . Relationship between central sympathetic drive and magnetic resonance imaging-determined left ventricular mass in essential hypertension. Circulation 2007; 115 (15): 1999–2005.

    PubMed  PubMed Central  Google Scholar 

  43. Lown B, Verrier RL . Neural activity and ventricular fibrillation. N Engl J Med 1976; 294 (21): 1165–1170.

    CAS  PubMed  Google Scholar 

  44. Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP . Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 1990; 322 (22): 1561–1566.

    CAS  PubMed  Google Scholar 

  45. Dao HH, Lemay J, de Champlain J, deBlois D, Moreau P . Norepinephrine-induced aortic hyperplasia and extracellular matrix deposition are endothelin-dependent. J Hypertens 2001; 19 (11): 1965–1973.

    CAS  PubMed  Google Scholar 

  46. Paton JF, Dickinson CJ, Mitchell G . Harvey Cushing and the regulation of blood pressure in giraffe, rat and man: introducing ‘Cushing's mechanism’. Exp Physiol 2009; 94 (1): 11–17.

    CAS  PubMed  Google Scholar 

  47. Harrap SB . Angiotensin converting enzyme inhibitors, regional vascular hemodynamics, and the development and prevention of experimental genetic hypertension. Am J Hypertens 1991; 4 (3 Part 2): 212S–216S.

    CAS  PubMed  Google Scholar 

  48. Harrap SB, Van der Merwe WM, Griffin SA, Macpherson F, Lever AF . Brief angiotensin converting enzyme inhibitor treatment in young spontaneously hypertensive rats reduces blood pressure long-term. Hypertension 1990; 16 (6): 603–614.

    CAS  PubMed  Google Scholar 

  49. Blacher J, Asmar R, Djane S, London GM, Safar ME . Aortic pulse wave velocity as a marker of cardiovascular risk in hypertensive patients. Hypertension 1999; 33 (5): 1111–1117.

    CAS  PubMed  Google Scholar 

  50. Gedikli O, Kiris A, Ozturk S, Baltaci D, Karaman K, Durmus I et al. Effects of prehypertension on arterial stiffness and wave reflections. Clin Exp Hypertens 2010; 32 (2): 84–89.

    PubMed  Google Scholar 

  51. Swierblewska E, Hering D, Kara T, Kunicka K, Kruszewski P, Bieniaszewski L et al. An independent relationship between muscle sympathetic nerve activity and pulse wave velocity in normal humans. J Hypertens 2010; 28 (5): 979–984.

    CAS  PubMed  Google Scholar 

  52. Grassi G, Giannattasio C, Failla M, Pesenti A, Peretti G, Marinoni E et al. Sympathetic modulation of radial artery compliance in congestive heart failure. Hypertension 1995; 26 (2): 348–354.

    CAS  PubMed  Google Scholar 

  53. Kaplan JR, Manuck SB . Using ethological principles to study psychosocial influences on coronary atherosclerosis in monkeys. Acta Physiol Scand Suppl 1997; 640: 96–99.

    CAS  PubMed  Google Scholar 

  54. Hijmering ML, Stroes ES, Olijhoek J, Hutten BA, Blankestijn PJ, Rabelink TJ . Sympathetic activation markedly reduces endothelium-dependent, flow-mediated vasodilation. J Am Coll Cardiol 2002; 39 (4): 683–688.

    PubMed  Google Scholar 

  55. Miyagawa K, Ohashi M, Yamashita S, Kojima M, Sato K, Ueda R et al. Increased oxidative stress impairs endothelial modulation of contractions in arteries from spontaneously hypertensive rats. J Hypertens 2007; 25 (2): 415–421.

    CAS  PubMed  Google Scholar 

  56. Lembo G, Vecchione C, Izzo R, Fratta L, Fontana D, Marino G et al. Noradrenergic vascular hyper-responsiveness in human hypertension is dependent on oxygen free radical impairment of nitric oxide activity. Circulation 2000; 102 (5): 552–557.

    CAS  PubMed  Google Scholar 

  57. Perticone F, Ceravolo R, Pujia A, Ventura G, Iacopino S, Scozzafava A et al. Prognostic significance of endothelial dysfunction in hypertensive patients. Circulation 2001; 104 (2): 191–196.

    CAS  PubMed  Google Scholar 

  58. Landsberg L . Insulin-mediated sympathetic stimulation: role in the pathogenesis of obesity-related hypertension (or, how insulin affects blood pressure, and why). J Hypertens 2001; 19 (3 Part 2): 523–528.

    CAS  PubMed  Google Scholar 

  59. DiBona GF, Esler M . Translational medicine: the antihypertensive effect of renal denervation. Am J Physiol Regul Integr Comp Physiol 2010; 298 (2): R245–R253.

    CAS  PubMed  Google Scholar 

  60. Elenkov IJ, Wilder RL, Chrousos GP, Vizi ES . The sympathetic nerve—an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev 2000; 52 (4): 595–638.

    CAS  PubMed  Google Scholar 

  61. Barretto AC, Santos AC, Munhoz R, Rondon MU, Franco FG, Trombetta IC et al. Increased muscle sympathetic nerve activity predicts mortality in heart failure patients. Int J Cardiol 2008; 135 (3): 302–307.

    PubMed  Google Scholar 

  62. Cohn JN, Levine TB, Olivari MT, Garberg V, Lura D, Francis GS et al. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med 1984; 311 (13): 819–823.

    CAS  PubMed  Google Scholar 

  63. Zoccali C, Mallamaci F, Parlongo S, Cutrupi S, Benedetto FA, Tripepi G et al. Plasma norepinephrine predicts survival and incident cardiovascular events in patients with end-stage renal disease. Circulation 2002; 105 (11): 1354–1359.

    CAS  PubMed  Google Scholar 

  64. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo Jr JL et al. Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension 2003; 42 (6): 1206–1252.

    CAS  PubMed  Google Scholar 

  65. Williams B, Poulter NR, Brown MJ, Davis M, McInnes GT, Potter JF et al. Guidelines for management of hypertension: report of the fourth working party of the British Hypertension Society, 2004-BHS IV. J Hum Hypertens 2004; 18 (3): 139–185.

    CAS  PubMed  Google Scholar 

  66. Catt KJ, Cran E, Zimmet PZ, Best JB, Cain MD, Coghlan JP . Angiotensin II blood-levels in human hypertension. Lancet 1971; 1 (7697): 459–464.

    CAS  PubMed  Google Scholar 

  67. Ferrario CM . Neurogenic actions of angiotensin II. Hypertension 1983; 5 (6 Part 3): V73–V79.

    CAS  PubMed  Google Scholar 

  68. Miyajima E, Shigemasa T, Yamada Y, Tochikubo O, Ishii M . Angiotensin II blunts, while an angiotensin-converting enzyme inhibitor augments, reflex sympathetic inhibition in humans. Clin Exp Pharmacol Physiol 1999; 26 (10): 797–802.

    CAS  PubMed  Google Scholar 

  69. Grassi G, Turri C, Dell’Oro R, Stella ML, Bolla GB, Mancia G . Effect of chronic angiotensin converting enzyme inhibition on sympathetic nerve traffic and baroreflex control of the circulation in essential hypertension. J Hypertens 1998; 16 (12 Part 1): 1789–1796.

    CAS  PubMed  Google Scholar 

  70. Krum H, Lambert E, Windebank E, Campbell DJ, Esler M . Effect of angiotensin II receptor blockade on autonomic nervous system function in patients with essential hypertension. Am J Physiol Heart Circ Physiol 2006; 290 (4): H1706–H1712.

    CAS  PubMed  Google Scholar 

  71. Wallin BG, Sundlof G, Stromgren E, Aberg H . Sympathetic outflow to muscles during treatment of hypertension with metoprolol. Hypertension 1984; 6 (4): 557–562.

    CAS  PubMed  Google Scholar 

  72. Gourine A, Bondar SI, Spyer KM, Gourine AV . Beneficial effect of the central nervous system beta-adrenoceptor blockade on the failing heart. Circ Res 2008; 102 (6): 633–636.

    CAS  PubMed  Google Scholar 

  73. Menon DV, Arbique D, Wang Z, Adams-Huet B, Auchus RJ, Vongpatanasin W . Differential effects of chlorthalidone versus spironolactone on muscle sympathetic nerve activity in hypertensive patients. J Clin Endocrinol Metab 2009; 94 (4): 1361–1366.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Grassi G, Seravalle G, Turri C, Bolla G, Mancia G . Short-versus long-term effects of different dihydropyridines on sympathetic and baroreflex function in hypertension. Hypertension 2003; 41 (3): 558–562.

    CAS  PubMed  Google Scholar 

  75. Fu Q, Zhang R, Witkowski S, Arbab-Zadeh A, Prasad A, Okazaki K et al. Persistent sympathetic activation during chronic antihypertensive therapy: a potential mechanism for long term morbidity? Hypertension 2005; 45 (4): 513–521.

    CAS  PubMed  Google Scholar 

  76. DeQuattro V, Li D . Sympatholytic therapy in primary hypertension: a user friendly role for the future. J Hum Hypertens 2002; 16 (Suppl 1): S118–S123.

    CAS  PubMed  Google Scholar 

  77. Duale H, Waki H, Howorth P, Kasparov S, Teschemacher AG, Paton JF . Restraining influence of A2 neurons in chronic control of arterial pressure in spontaneously hypertensive rats. Cardiovasc Res 2007; 76 (1): 184–193.

    CAS  PubMed  Google Scholar 

  78. Amery AK, Bossaert H, Fagard RH, Verstraete M . Clonidine versus methyldopa. A double blind cross-over study comparing side effects of clonidine and methyldopa administered together with chlorthalidone at a dosage producing the same blood pressure lowering effect. Acta Cardiol 1972; 21 (1): 82–99.

    CAS  PubMed  Google Scholar 

  79. Wenzel RR, Spieker L, Qui S, Shaw S, Luscher TF, Noll G . I1-imidazoline agonist moxonidine decreases sympathetic nerve activity and blood pressure in hypertensives. Hypertension 1998; 32 (6): 1022–1027.

    CAS  PubMed  Google Scholar 

  80. Esler M, Lux A, Jennings G, Hastings J, Socratous F, Lambert G . Rilmenidine sympatholytic activity preserves mental stress, orthostatic sympathetic responses and adrenaline secretion. J Hypertens 2004; 22 (8): 1529–1534.

    CAS  PubMed  Google Scholar 

  81. Tipton CM . Concerning postexercise hypotension. Exerc Sport Sci Rev 2011; 39 (2): 109.

    PubMed  Google Scholar 

  82. American College of Sports Medicine. Position stand. Physical activity, physical fitness, and hypertension. Med Sci Sports Exerc 1993; 25 (10): i–x.

    Google Scholar 

  83. Laterza MC, de Matos LD, Trombetta IC, Braga AM, Roveda F, Alves MJ et al. Exercise training restores baroreflex sensitivity in never-treated hypertensive patients. Hypertension 2007; 49 (6): 1298–1306.

    CAS  PubMed  Google Scholar 

  84. Zucker IH, Patel KP, Schultz HD, Li YF, Wang W, Pliquett RU . Exercise training and sympathetic regulation in experimental heart failure. Exerc Sport Sci Rev 2004; 32 (3): 107–111.

    PubMed  Google Scholar 

  85. Straznicky NE, Lambert EA, Nestel PJ, McGrane MT, Dawood T, Schlaich MP et al. Sympathetic neural adaptation to hypocaloric diet with or without exercise training in obese metabolic syndrome subjects. Diabetes 2010; 59 (1): 71–79.

    PubMed  Google Scholar 

  86. Trombetta IC, Batalha LT, Rondon MU, Laterza MC, Kuniyoshi FH, Gowdak MM et al. Weight loss improves neurovascular and muscle metaboreflex control in obesity. Am J Physiol Heart Circ Physiol 2003; 285 (3): H974–H982.

    CAS  PubMed  Google Scholar 

  87. Mancia G, Bousquet P, Elghozi JL, Esler M, Grassi G, Julius S et al. The sympathetic nervous system and the metabolic syndrome. J Hypertens 2007; 25 (5): 909–920.

    CAS  PubMed  Google Scholar 

  88. Lucini D, Di Fede G, Parati G, Pagani M . Impact of chronic psychosocial stress on autonomic cardiovascular regulation in otherwise healthy subjects. Hypertension 2005; 46 (5): 1201–1206.

    CAS  PubMed  Google Scholar 

  89. Rainforth MV, Schneider RH, Nidich SI, Gaylord-King C, Salerno JW, Anderson JW . Stress reduction programs in patients with elevated blood pressure: a systematic review and meta-analysis. Curr Hypertens Rep 2007; 9 (6): 520–528.

    PubMed  PubMed Central  Google Scholar 

  90. Oneda B, Ortega KC, Gusmao JL, Araujo TG, Mion Jr D . Sympathetic nerve activity is decreased during device-guided slow breathing. Hypertens Res 2010; 33 (7): 708–712.

    PubMed  Google Scholar 

  91. Viskoper R, Shapira I, Priluck R, Mindlin R, Chornia L, Laszt A et al. Nonpharmacologic treatment of resistant hypertensives by device-guided slow breathing exercises. Am J Hypertens 2003; 16 (6): 484–487.

    PubMed  Google Scholar 

  92. Anderson DE, McNeely JD, Windham BG . Regular slow-breathing exercise effects on blood pressure and breathing patterns at rest. J Hum Hypertens 2010; 24 (12): 807–813.

    CAS  PubMed  Google Scholar 

  93. Altena MR, Kleefstra N, Logtenberg SJ, Groenier KH, Houweling ST, Bilo HJ . Effect of device-guided breathing exercises on blood pressure in patients with hypertension: a randomized controlled trial. Blood Press 2009; 18 (5): 273–279.

    PubMed  Google Scholar 

  94. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J . Global burden of hypertension: analysis of worldwide data. Lancet 2005; 365 (9455): 217–223.

    PubMed  Google Scholar 

  95. Plump A . Accelerating the pulse of cardiovascular R&D. Nat Rev Drug Discov 2010; 9 (11): 823–824.

    CAS  PubMed  Google Scholar 

  96. Fisher JP, Fadel PJ . Therapeutic strategies for targeting excessive central sympathetic activation in human hypertension. Exp Physiol 2010; 95 (5): 572–580.

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Schlaich MP, Krum H, Esler MD . New therapeutic approaches to resistant hypertension. Curr Hypertens Rep 2010; 12 (4): 296–302.

    CAS  PubMed  Google Scholar 

  98. Schlaich MP, Sobotka PA, Krum H, Lambert E, Esler MD . Renal sympathetic-nerve ablation for uncontrolled hypertension. N Engl J Med 2009; 361 (9): 932–934.

    CAS  PubMed  Google Scholar 

  99. Bilgutay AM, Lillehei CW . Treatment of Hypertension with an implantable electronic device. JAMA 1965; 191: 649–653.

    CAS  PubMed  Google Scholar 

  100. Epstein SE, Beiser GD, Goldstein RE, Stampfer M, Wechsler AS, Glick G et al. Circulatory effects of electrical stimulation of the carotid sinus nerves in man. Circulation 1969; 40 (3): 269–276.

    CAS  PubMed  Google Scholar 

  101. Illig KA, Levy M, Sanchez L, Trachiotis GD, Shanley C, Irwin E et al. An implantable carotid sinus stimulator for drug-resistant hypertension: surgical technique and short-term outcome from the multicenter phase II Rheos feasibility trial. J Vasc Surg 2006; 44 (6): 1213–1218.

    PubMed  Google Scholar 

  102. Lohmeier TE, Barrett AM, Irwin ED . Prolonged activation of the baroreflex: a viable approach for the treatment of hypertension? Curr Hypertens Rep 2005; 7 (3): 193–198.

    PubMed  Google Scholar 

  103. Scheffers IJ, Kroon AA, Schmidli J, Jordan J, Tordoir JJ, Mohaupt MG et al. Novel baroreflex activation therapy in resistant hypertension: results of a European multi-center feasibility study. J Am Coll Cardiol 2010; 56 (15): 1254–1258.

    PubMed  Google Scholar 

  104. Heusser K, Tank J, Engeli S, Diedrich A, Menne J, Eckert S et al. Carotid baroreceptor stimulation, sympathetic activity, baroreflex function, and blood pressure in hypertensive patients. Hypertension 2010; 55 (3): 619–626.

    CAS  PubMed  Google Scholar 

  105. Thrasher TN . Unloading arterial baroreceptors causes neurogenic hypertension. Am J Physiol Regul Integr Comp Physiol 2002; 282 (4): R1044–R1053.

    CAS  PubMed  Google Scholar 

  106. Lohmeier TE, Iliescu R, Dwyer TM, Irwin ED, Cates AW, Rossing MA . Sustained suppression of sympathetic activity and arterial pressure during chronic activation of the carotid baroreflex. Am J Physiol Heart Circ Physiol 2010; 299 (2): H402–H409.

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Yao T, Thoren P . Characteristics of brachiocephalic and carotid sinus baroreceptors with non-medullated afferents in rabbit. Acta Physiol Scand 1983; 117 (1): 1–8.

    CAS  PubMed  Google Scholar 

  108. Munch PA, Andresen MC, Brown AM . Rapid resetting of aortic baroreceptors in vitro. Am J Physiol 1983; 244 (5): H672–H680.

    CAS  PubMed  Google Scholar 

  109. Pereira EA, Wang S, Paterson DJ, Stein JF, Aziz TZ, Green AL . Sustained reduction of hypertension by deep brain stimulation. J Clin Neurosci 2010; 17 (1): 124–127.

    PubMed  Google Scholar 

  110. Patel NK, Javed S, Khan S, Papouchado M, Malizia AL, Pickering AE et al. Deep brain stimulation relieves refractory hypertension. Neurology 2011; 76 (4): 405–407.

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Carrive P, Bandler R . Viscerotopic organization of neurons subserving hypotensive reactions within the midbrain periaqueductal grey: a correlative functional and anatomical study. Brain Res 1991; 541 (2): 206–215.

    CAS  PubMed  Google Scholar 

  112. Dampney RA . Functional organization of central pathways regulating the cardiovascular system. Physiol Rev 1994; 74 (2): 323–364.

    CAS  PubMed  Google Scholar 

  113. Tai MH, Wang LL, Wu KL, Chan JY . Increased superoxide anion in rostral ventrolateral medulla contributes to hypertension in spontaneously hypertensive rats via interactions with nitric oxide. Free Radic Biol Med 2005; 38 (4): 450–462.

    CAS  PubMed  Google Scholar 

  114. Oliveira-Sales EB, Dugaich AP, Carillo BA, Abreu NP, Boim MA, Martins PJ et al. Oxidative stress contributes to renovascular hypertension. Am J Hypertens 2008; 21 (1): 98–104.

    CAS  PubMed  Google Scholar 

  115. Oliveira-Sales EB, Colombari DS, Davisson RL, Kasparov S, Hirata AE, Campos RR et al. Kidney-induced hypertension depends on superoxide signaling in the rostral ventrolateral medulla. Hypertension 2010; 56 (2): 290–296.

    CAS  PubMed  Google Scholar 

  116. Griendling KK, Sorescu D, Ushio-Fukai M . NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res 2000; 86 (5): 494–501.

    CAS  PubMed  Google Scholar 

  117. Gao L, Wang W, Li YL, Schultz HD, Liu D, Cornish KG et al. Sympathoexcitation by central ANG II: roles for AT1 receptor upregulation and NAD(P)H oxidase in RVLM. Am J Physiol Heart Circ Physiol 2005; 288 (5): H2271–H2279.

    CAS  PubMed  Google Scholar 

  118. Chan SH, Hsu KS, Huang CC, Wang LL, Ou CC, Chan JY . NADPH oxidase-derived superoxide anion mediates angiotensin II-induced pressor effect via activation of p38 mitogen-activated protein kinase in the rostral ventrolateral medulla. Circ Res 2005; 97 (8): 772–780.

    CAS  PubMed  Google Scholar 

  119. Simpson JB . The circumventricular organs and the central actions of angiotensin. Neuroendocrinology 1981; 32 (4): 248–256.

    CAS  PubMed  Google Scholar 

  120. Bickerton RK, Buckley JP . Evidence for a central mechanism in angiotensin induced hypertension. Proc Soc Exp Biol Med 1961; 106: 14.

    Google Scholar 

  121. Guzik TJ, Hoch NE, Brown KA, McCann LA, Rahman A, Dikalov S et al. Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction. J Exp Med 2007; 204 (10): 2449–2460.

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Hoch NE, Guzik TJ, Chen W, Deans T, Maalouf SA, Gratze P et al. Regulation of T-cell function by endogenously produced angiotensin II. Am J Physiol Regul Integr Comp Physiol 2009; 296 (2): R208–R216.

    CAS  PubMed  Google Scholar 

  123. Sesso HD, Buring JE, Rifai N, Blake GJ, Gaziano JM, Ridker PM . C-reactive protein and the risk of developing hypertension. JAMA 2003; 290 (22): 2945–2951.

    CAS  PubMed  Google Scholar 

  124. Libby P, Ridker PM, Maseri A . Inflammation and atherosclerosis. Circulation 2002; 105 (9): 1135–1143.

    CAS  PubMed  Google Scholar 

  125. Marvar PJ, Thabet SR, Guzik TJ, Lob HE, McCann LA, Weyand C et al. Central and peripheral mechanisms of T-lymphocyte activation and vascular inflammation produced by angiotensin II-induced hypertension. Circ Res 2010; 107 (2): 263–270.

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Waki H, Liu B, Miyake M, Katahira K, Murphy D, Kasparov S et al. Junctional adhesion molecule-1 is upregulated in spontaneously hypertensive rats: evidence for a prohypertensive role within the brain stem. Hypertension 2007; 49 (6): 1321–1327.

    CAS  PubMed  Google Scholar 

  127. Ong KL, Leung RY, Wong LY, Cherny SS, Sham PC, Lam TH et al. Association of F11 receptor gene polymorphisms with central obesity and blood pressure. J Intern Med 2008; 263 (3): 322–332.

    CAS  PubMed  Google Scholar 

  128. Kang YM, Ma Y, Zheng JP, Elks C, Sriramula S, Yang ZM et al. Brain nuclear factor-kappa B activation contributes to neurohumoral excitation in angiotensin II-induced hypertension. Cardiovasc Res 2009; 82 (3): 503–512.

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Sriramula S, Haque M, Majid DS, Francis J . Involvement of tumor necrosis factor-alpha in angiotensin II-mediated effects on salt appetite, hypertension, and cardiac hypertrophy. Hypertension 2008; 51 (5): 1345–1351.

    CAS  PubMed  Google Scholar 

  130. Shi P, Diez-Freire C, Jun JY, Qi Y, Katovich MJ, Li Q et al. Brain microglial cytokines in neurogenic hypertension. Hypertension 2010; 56 (2): 297–303.

    CAS  PubMed  Google Scholar 

  131. Takagishi M, Waki H, Bhuiyan ME, Gouraud SS, Kohsaka A, Cui H et al. IL-6 microinjected in the nucleus tractus solitarii attenuates cardiac baroreceptor reflex function in rats. Am J Physiol Regul Integr Comp Physiol 2010; 298 (1): R183–R190.

    CAS  PubMed  Google Scholar 

  132. Waki H, Gouraud SS, Maeda M, Paton JF . Gene expression profiles of major cytokines in the nucleus tractus solitarii of the spontaneously hypertensive rat. Auton Neurosci 2008; 142 (1–2): 40–44.

    CAS  PubMed  Google Scholar 

  133. Waki H, Gouraud SS, Maeda M, Paton JF . Specific inflammatory condition in nucleus tractus solitarii of the SHR: novel insight for neurogenic hypertension? Auton Neurosci 2008; 142 (1–2): 25–31.

    CAS  PubMed  Google Scholar 

  134. Helwig BG, Craig RA, Fels RJ, Blecha F, Kenney MJ . Central nervous system administration of interleukin-6 produces splenic sympathoexcitation. Auton Neurosci 2008; 141 (1–2): 104–111.

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Niijima A, Hori T, Aou S, Oomura Y . The effects of interleukin-1 beta on the activity of adrenal, splenic and renal sympathetic nerves in the rat. J Auton Nerv Syst 1991; 36 (3): 183–192.

    CAS  PubMed  Google Scholar 

  136. Gouraud SS, Waki H, Bhuiyan ME, Takagishi M, Cui H, Kohsaka A et al. Down-regulation of chemokine Ccl5 gene expression in the NTS of SHR may be pro-hypertensive. J Hypertens 2011; 29 (4): 732–740.

    CAS  PubMed  Google Scholar 

  137. Zhang ZH, Wei SG, Francis J, Felder RB . Cardiovascular and renal sympathetic activation by blood-borne TNF-alpha in rat: the role of central prostaglandins. Am J Physiol Regul Integr Comp Physiol 2003; 284 (4): R916–R927.

    CAS  PubMed  Google Scholar 

  138. Dickinson CJ, Thomson AD . A post mortem study of the main cerebral arteries with special reference to their possible role in blood pressure regulation. Clin Sci 1960; 19: 513–538.

    CAS  PubMed  Google Scholar 

  139. Wang G, Zhou P, Repucci MA, Golanov EV, Reis DJ . Specific actions of cyanide on membrane potential and voltage-gated ion currents in rostral ventrolateral medulla neurons in rat brainstem slices. Neurosci Lett 2001; 309 (2): 125–129.

    CAS  PubMed  Google Scholar 

  140. Braga VA, Paton JF, Machado BH . Ischaemia-induced sympathoexcitation in spinalyzed rats. Neurosci Lett 2007; 415 (1): 73–76.

    CAS  PubMed  Google Scholar 

  141. Smith PA, Meaney JF, Graham LN, Stoker JB, Mackintosh AF, Mary DA et al. Relationship of neurovascular compression to central sympathetic discharge and essential hypertension. J Am Coll Cardiol 2004; 43 (8): 1453–1458.

    PubMed  Google Scholar 

  142. Naraghi R, Gaab MR, Walter GF, Kleineberg B . Arterial hypertension and neurovascular compression at the ventrolateral medulla. A comparative microanatomical and pathological study. J Neurosurg 1992; 77 (1): 103–112.

    CAS  PubMed  Google Scholar 

  143. Cates MJ, Steed PJ, Abdala APL, Langton PD, Paton JFR . Elevated vertebrobasilar artery resistance in neonatal spontaneously hypertensive rats. J Appl Physiol 2011 (in press).

  144. Osborn JW . Hypothesis: set-points and long-term control of arterial pressure. A theoretical argument for a long-term arterial pressure control system in the brain rather than the kidney. Clin Exp Pharmacol Physiol 2005; 32 (5–6): 384–393.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the support of the British Heart Foundation and the National Institutes of Health (HL033610). JFR Paton is a recipient of a Royal Society Wolfson Research Merit Award.

Author information

Authors and Affiliations

  1. School of Sport and Exercise Sciences, College of Life & Environmental Sciences, University of Birmingham, Birmingham, UK

    J P Fisher

  2. School of Physiology & Pharmacology, Bristol Heart Institute, Medical Sciences Building, University of Bristol, Bristol, UK

    J F R Paton

Authors
  1. J P Fisher
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J F R Paton
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to J P Fisher or J F R Paton.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fisher, J., Paton, J. The sympathetic nervous system and blood pressure in humans: implications for hypertension. J Hum Hypertens 26, 463–475 (2012). https://doi.org/10.1038/jhh.2011.66

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jhh.2011.66

Keywords

This article is cited by

Search

Advanced search

Quick links