Skip to main content
SpringerLink
Log in

Sympathetic neural mechanisms in human hypertension

  • Published:
Current Hypertension Reports Aims and scope Submit manuscript

Abstract

Compared with substantial clinical research on the renin-angiotensin-aldosterone system (RAAS), much less is known about the importance of the sympathetic nervous system as a therapeutic target to slow the initiation and progression of human hypertension. Using microelectrode recordings of sympathetic activity and radiotracer measurements of regional norepinephrine spillover in hypertensive patients, recent research has advanced several provocative findings with novel—but still largely potential—therapeutic implications for clinical hypertension. These include a stronger scientific rationale for using 1) combined α/β-blockers in the early phases of primary hypertension and obesity-related hypertension; 2) RAAS blockers as central sympatholytics in hypertension associated with chronic kidney disease; and 3) a higher dialysis dose—either nocturnal or short daily hemodialysis—to reduce uremic stimulation of a blood pressure-raising reflex arising in the failing kidneys. New outcomes trials are needed if we are to translate this largely theoretical body of research into clinical practice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. National Institute for Health and Clinical Excellence: Hypertension: Management in adults in primary care: pharmacological update. Available at http://www.nice.org.uk/nicemedia/pdf/HypertensionGuide.pdf. Accessed January 2008.

  2. Victor RG, Kaplan NM: Systemic hypertension: mechanisms and diagnosis. In Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine, edn 8. Edited by Libby P, Bonow RO, Mann DL, Zipes DP. Philadelphia: Saunders/Elsevier; 2007:1027–1046.

    Google Scholar 

  3. Schlaich MP, Lambert E, Kaye DM, et al.: Sympathetic augmentation in hypertension: role of nerve firing, norepinephrine reuptake, and angiotensin neuromodulation. Hypertension 2004, 43:169–175.

    Article  PubMed  CAS  Google Scholar 

  4. Esler M, Lambert E: Reduced HRV and baroreflex sensitivity as universally applicable cardiovascular “risk factors”; waiting for the bubble to burst. Clin Auton Res 2003, 13:170–172.

    PubMed  Google Scholar 

  5. Taylor JA, Studinger P: Counterpoint: cardiovascular variability is not an index of autonomic control of the circulation. J Appl Physiol 2006, 101:678–681.

    Article  PubMed  CAS  Google Scholar 

  6. Vongpatanasin W, Taylor JA, Victor RG: Effects of cocaine on heart rate variability in healthy subjects. Am J Cardiol 2004, 93:385–388.

    Article  PubMed  CAS  Google Scholar 

  7. Vallbo AB, Hagbarth KE, Wallin BG: Microneurography: how the technique developed and its role in the investigation of the sympathetic nervous system. J Appl Physiol 2004, 96:1262–1269.

    Article  PubMed  Google Scholar 

  8. Wallin BG, Charkoudian N: Sympathetic neural control of integrated cardiovascular function: insights from measurement of human sympathetic nerve activity. Muscle Nerve 2007, 36:595–614.

    Article  PubMed  CAS  Google Scholar 

  9. Esler M, Straznicky N, Eikelis N, et al.: Mechanisms of sympathetic activation in obesity-related hypertension. Hypertension 2006, 48:787–796.

    Article  PubMed  CAS  Google Scholar 

  10. Guyenet PG: The sympathetic control of blood pressure. Nat Rev Neurosci 2006, 7:335–346.

    Article  PubMed  CAS  Google Scholar 

  11. Grassi G, Seravalle G, Trevano FQ, et al.: Neurogenic abnormalities in masked hypertension. Hypertension 2007, 50:537–542.

    Article  PubMed  CAS  Google Scholar 

  12. Pickering TG, Eguchi K, Kario K: Masked hypertension: a review. Hypertens Res 2007, 30:479–488.

    Article  PubMed  Google Scholar 

  13. Fu Q, Zhang R, Witkowski S, et al.: Persistent sympathetic activation during chronic antihypertensive therapy: a potential mechanism for long term morbidity? Hypertension 2005, 45:513–521.

    Article  PubMed  CAS  Google Scholar 

  14. Mancia G, De BG, Dominiczak A, et al.: 2007 Guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2007, 28:1462–1536.

    PubMed  Google Scholar 

  15. Bakris GL, Fonseca V, Katholi RE, et al.: Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: a randomized controlled trial. JAMA 2004, 292:2227–2236.

    Article  PubMed  CAS  Google Scholar 

  16. Koomans HA, Blankestijn PJ, Joles JA: Sympathetic hyperactivity in chronic renal failure: a wake-up call. J Am Soc Nephrol 2004, 15:524–537.

    Article  PubMed  Google Scholar 

  17. Kotanko P: Cause and consequences of sympathetic hyperactivity in chronic kidney disease. Blood Purif 2006, 24:95–99.

    Article  PubMed  Google Scholar 

  18. Converse RL Jr, Jacobsen TN, Toto RD, et al.: Sympathetic overactivity in patients with chronic renal failure. N Engl J Med 1992, 327:1912–1918.

    PubMed  Google Scholar 

  19. Campese VM, Krol E: Neurogenic factors in renal hypertension. Curr Hypertens Rep 2002, 4:256–260.

    Article  PubMed  Google Scholar 

  20. Chan CT, Harvey PJ, Picton P, et al.: Short-term blood pressure, noradrenergic, and vascular effects of nocturnal home hemodialysis. Hypertension 2003, 42:925–931.

    Article  PubMed  CAS  Google Scholar 

  21. Chan CT, Jain V, Picton P, et al.: Nocturnal hemodialysis increases arterial baroreflex sensitivity and compliance and normalizes blood pressure of hypertensive patients with end-stage renal disease. Kidney Int 2005, 68:338–344.

    Article  PubMed  Google Scholar 

  22. Zilch O, Vos PF, Oey PL, et al.: Sympathetic hyperactivity in haemodialysis patients is reduced by short daily haemodialysis. J Hypertension 2007, 25:1285–1289.

    Article  CAS  Google Scholar 

  23. Campese VM, Shaohua Y, Huiquin Z: Oxidative stress mediates angiotensin II-dependent stimulation of sympathetic nerve activity. Hypertension 2005, 46:533–539.

    Article  PubMed  CAS  Google Scholar 

  24. Neumann J, Ligtenberg G, Klein II, et al.: Sympathetic hyperactivity in chronic kidney disease: pathogenesis, clinical relevance, and treatment. Kidney Int 2004, 65:1568–1576.

    Article  PubMed  Google Scholar 

  25. Neumann J, Ligtenberg G, Klein IH, et al.: Sympathetic hyperactivity in hypertensive chronic kidney disease patients is reduced during standard treatment. Hypertension 2007, 49:506–510.

    Article  PubMed  CAS  Google Scholar 

  26. Neumann J, Ligtenberg G, Oey L, et al.: Moxonidine normalizes sympathetic hyperactivity in patients with eprosartan-treated chronic renal failure. J Am Soc Nephrol 2004, 15:2902–2907.

    Article  PubMed  CAS  Google Scholar 

  27. Biaggioni I: The sympathetic nervous system and blood volume regulation: lessons from autonomic failure patients. Am J Med Sci 2007, 334:61–64.

    Article  PubMed  Google Scholar 

  28. Biaggioni I: Should we target the sympathetic nervous system in the treatment of obesity-associated hypertension? Hypertension 2008, 51:168–171.

    Article  PubMed  CAS  Google Scholar 

  29. Mancia G, Bousquet P, Elghozi JL, et al.: The sympathetic nervous system and the metabolic syndrome. J Hypertens 2007, 25:909–920.

    Article  PubMed  CAS  Google Scholar 

  30. Landsberg L: A teleological view of obesity, diabetes and hypertension. Clin Exp Pharmacol Physiol 2006, 33:863–867.

    Article  PubMed  CAS  Google Scholar 

  31. Shibao C, Gamboa A, Diedrich A, et al.: Autonomic contribution to blood pressure and metabolism in obesity. Hypertension 2007, 49:27–33.

    Article  PubMed  CAS  Google Scholar 

  32. Narkiewicz K, Wolf J, Lopez-Jimenez F, Somers VK: Obstructive sleep apnea and hypertension. Curr Cardiol Rep 2005, 7:435–440.

    Article  PubMed  Google Scholar 

  33. Huang J, Tamisier R, Ji E, et al.: Chronic intermittent hypoxia modulates nNOS mRNA and protein expression in the rat hypothalamus. Respir Physiol Neurobiol 2007, 158:30–38.

    Article  PubMed  CAS  Google Scholar 

  34. Thomas GD, Zhang W, Victor RG: Nitric oxide deficiency as a cause of clinical hypertension: promising new drug targets for refractory hypertension. JAMA 2001, 285:2055–2057.

    Article  PubMed  CAS  Google Scholar 

  35. Young WF Jr: Adrenal causes of hypertension: pheochromocytoma and primary aldosteronism. Rev Endocr Metab Disord 2007, 8:309–320.

    Article  PubMed  CAS  Google Scholar 

  36. Alajmi M, Mulgrew AT, Fox J, et al.: Impact of continuous positive airway pressure therapy on blood pressure in patients with obstructive sleep apnea hypopnea: a meta-analysis of randomized controlled trials. Lung 2007, 185:67–72.

    Article  PubMed  CAS  Google Scholar 

  37. Bazzano LA, Khan Z, Reynolds K, He J: Effect of nocturnal nasal continuous positive airway pressure on blood pressure in obstructive sleep apnea. Hypertension 2007, 50:417–423.

    Article  PubMed  CAS  Google Scholar 

  38. Haentjens P, Van MA, Moscariello A, et al.: The impact of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea syndrome: evidence from a meta-analysis of placebo-controlled randomized trials. Arch Intern Med 2007, 167:757–764.

    Article  PubMed  Google Scholar 

  39. Usui K, Bradley TD, Spaak J, et al.: Inhibition of awake sympathetic nerve activity of heart failure patients with obstructive sleep apnea by nocturnal continuous positive airway pressure. J Am Coll Cardiol 2005, 45:2008–2011.

    Article  PubMed  Google Scholar 

  40. Donadio V, Liguori R, Vetrugno R, et al.: Parallel changes in resting muscle sympathetic nerve activity and blood pressure in a hypertensive OSAS patient demonstrate treatment efficacy. Clin Auton Res 2006, 16:235–239.

    Article  PubMed  Google Scholar 

  41. Phillips CL, Yang Q, Williams A, et al.: The effect of short-term withdrawal from continuous positive airway pressure therapy on sympathetic activity and markers of vascular inflammation in subjects with obstructive sleep apnoea. J Sleep Res 2007, 16:217–225.

    Article  PubMed  Google Scholar 

  42. Calhoun DA, Nishizaka MK, Zaman MA, Harding SM: Aldosterone excretion among subjects with resistant hypertension and symptoms of sleep apnea. Chest 2004, 125:112–117.

    Article  PubMed  CAS  Google Scholar 

  43. Pratt-Ubunama MN, Nishizaka MK, Boedefeld RL, et al.: Plasma aldosterone is related to severity of obstructive sleep apnea in subjects with resistant hypertension. Chest 2007, 131:453–459.

    Article  PubMed  CAS  Google Scholar 

  44. Pimenta E, Calhoun DA: Resistant hypertension and aldosteronism. Curr Hypertens Rep 2007, 9:353–359.

    Article  PubMed  CAS  Google Scholar 

  45. Shiota S, Ryan CM, Chiu KL, et al.: Alternations in upper airway cross-sectional area in response to lower body positive pressure in healthy subjects. Thorax 2007, 62:868–872.

    Article  PubMed  Google Scholar 

  46. Lambert E, Straznicky N, Schlaich M, et al.: Differing pattern of sympathoexcitation in normal-weight and obesity-related hypertension. Hypertension 2007, 50:862–868.

    Article  PubMed  CAS  Google Scholar 

  47. Lohmeier TE, Dwyer TM, Irwin ED, et al.: Prolonged activation of the baroreflex abolishes obesity-induced hypertension. Hypertension 2007, 49:1307–1314.

    Article  PubMed  CAS  Google Scholar 

  48. Filippone JD, Bisognano JD: Baroreflex stimulation in the treatment of hypertension. Curr Opin Nephrol Hypertens 2007, 16:403–408.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Internal Medicine, Hypertension Division, UT Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX, 75390, USA

    Ronald G. Victor

Authors
  1. Ronald G. Victor
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Moiz M. Shafiq
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ronald G. Victor.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Victor, R.G., Shafiq, M.M. Sympathetic neural mechanisms in human hypertension. Current Science Inc 10, 241–247 (2008). https://doi.org/10.1007/s11906-008-0045-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11906-008-0045-7

Keywords

Search

Navigation