Current Hypertension Reports

, Volume 15, Issue 4, pp 409–416 | Cite as

The Sympathetic Nervous System in Obesity Hypertension

Adrenal and Nervous System Mechanisms (S Oparil, Section Editor)

Abstract

Abundant evidence supports a role of the sympathetic nervous system in the pathogenesis of obesity-related hypertension. However, the nature and temporal progression of mechanisms underlying this sympathetically mediated hypertension are incompletely understood. Recent technological advances allowing direct recordings of renal sympathetic nerve activity (RSNA) in conscious animals, together with direct suppression of RSNA by renal denervation and reflex-mediated global sympathetic inhibition in experimental animals and human subjects have been especially valuable in elucidating these mechanisms. These studies strongly support the concept that increased RSNA is the critical mechanism by which increased central sympathetic outflow initiates and maintains reductions in renal excretory function, causing obesity hypertension. Potential determinants of renal sympathoexcitation and the differential mechanisms mediating the effects of renal-specific versus reflex-mediated, global sympathetic inhibition on renal hemodynamics and cardiac autonomic function are discussed. These differential mechanisms may impact the efficacy of current device-based approaches for hypertension therapy.

Keywords

Obesity Blood pressure Hypertension Sympathetic nervous system Renin-angiotensin system Renal nerves Renal denervation Baroreflex Baroreflex sensitivity Heart rate Heart rate variability Autonomic nervous system Glomerular filtration rate Renal function Cardiac arrhythmogenesis Device-based therapy 

References

Papers of particular interest, published recently, have been highlighted as: •Of Importance

  1. 1.
    Esler M, Straznicky N, Eikelis N, et al. Mechanisms of sympathetic activation in obesity-related hypertension. Hypertension. 2006;48:787–96.PubMedCrossRefGoogle Scholar
  2. 2.
    Hall JE, da Dilva AA, Brandon E, et al. Pathophysiology of obesity-induced hypertension and target organ damage. In: Lip GYH, Hall JE, editors. Comprehensive Hypertension. New York: Elsevier; 2007. p. 447–68.CrossRefGoogle Scholar
  3. 3.
    • Bisognano JD, Bakris G, Nadim MK, et al. Baroreflex activation therapy lowers blood pressure in patients with resistant hypertension: results from the double-blind, randomized, placebo-controlled Rheos Pivotal trial. J Am Coll Cardiol. 2011;58:765–73. The first randomized controlled trial investigating safety and efficacy of baroreflex activation therapy as treatment for resistant hypertension.PubMedCrossRefGoogle Scholar
  4. 4.
    Lohmeier TE, Iliescu R. Chronic lowering of blood pressure by carotid baroreflex activation. Mechanisms and potential for hypertension therapy. Hypertension. 2011;57:880–6.PubMedCrossRefGoogle Scholar
  5. 5.
    Schlaich MP, Sobotka PA, Krum H, et al. Renal denervation as a therapeutic approach for hypertension. Novel implications for an old concept. Hypertension. 2009;54:1195–201.PubMedCrossRefGoogle Scholar
  6. 6.
    • Esler MD, Krum H, Sobotka PA, et al. Renal sympathetic denervation in patients with treatment resistant hypertension (The Symplicity HTN-2 Trial): a randomized controlled trial. Lancet. 2011;376:1903–9. The first randomized controlled trial investigating safety and efficacy of catheter-based renal denervation as treatment for resistant hypertension.Google Scholar
  7. 7.
    Esler MD, Krum H, Schlaich M, et al. Renal sympathetic denervation for treatment of drug-resistant hypertension. One-year results from Symplicity HTN-2 randomized, controlled trial. Circulation. 2012;126:2976–82.PubMedCrossRefGoogle Scholar
  8. 8.
    Heusser K, Tank J, Engeli S, et al. Carotid baroreceptor stimulation, sympathetic activity, baroreflex function, and blood pressure in hypertensive patients. Hypertension. 2010;55:619–26.PubMedCrossRefGoogle Scholar
  9. 9.
    Lohmeier TE, Iliescu R, Dwyer TM, et al. Sustained suppression of sympathetic activity and arterial pressure during chronic activation of the carotid baroreflex. Am J Physiol Heart Circ Physiol. 2010;299:H402–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Hering D, Lambert EA, Marusic P, et al. Substantial reduction in single sympathetic nerve firing after renal denervation in patients with resistant hypertension. Hypertension. 2013;61:457–64.PubMedCrossRefGoogle Scholar
  11. 11.
    Brinkmann J, Heusser K, Schmidt BM, et al. Catheter-based renal nerve ablation and centrally generated sympathetic activity in difficult-to-control hypertensive patients. Prospective case studies. Hypertension. 2012;60:1485–90.PubMedCrossRefGoogle Scholar
  12. 12.
    Calhoun DA, Jones D, Textor S, et al. Resistant hypertension: diagnosis, evaluation, and treatment. Circulation. 2008;117:e510–26.PubMedCrossRefGoogle Scholar
  13. 13.
    Guyton AC. Arterial Pressure and Hypertension. Philadelphia, PA: Saunders; 1980.Google Scholar
  14. 14.
    Lohmeier TE, Hildebrandt DA, Warren S, et al. Recent insights into the interactions between the baroreflex and the kidneys in hypertension. Am J Physiol Regulatory Integrative Comp Physiol. 2005;288:R828–36.CrossRefGoogle Scholar
  15. 15.
    Lohmeier TE, Drummond HA. The baroreflex in the pathogenesis of hypertension. In: Lip GYH, Hall JE, editors. Comprehensive Hypertension. New York: Elsevier; 2007. p. 265–79.CrossRefGoogle Scholar
  16. 16.
    Lohmeier TE, Iliescu R. Lowering of blood pressure by chronic suppression of central sympathetic outflow: insight from prolonged baroreflex activation. J Appl Physiol. 2012;113:1652–8.PubMedCrossRefGoogle Scholar
  17. 17.
    DiBona GF, Kopp UC. Neural control of renal function. Physiol Rev. 1997;77:75–197.PubMedGoogle Scholar
  18. 18.
    Vaz M, Jennings G, Turner A. Regional sympathetic nervous activity and oxygen consumption in obese normotensive human subjects. Circulation. 1997;96:3423–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Rumantir MS, Vaz M, Jennings GL, et al. Neural mechanisms in human obesity-related hypertension. J Hypertens. 1999;17:1125–33.PubMedCrossRefGoogle Scholar
  20. 20.
    Kassab S, Kato T, Wilkins C, et al. Renal denervation attenuates the sodium retention and hypertension associated with obesity. Hypertension. 1995;25:893–7.PubMedCrossRefGoogle Scholar
  21. 21.
    • Lohmeier TE, Iliescu R, Liu B, et al. Systemic and renal-specific sympathoinhibition in obesity hypertension. Hypertension. 2012;59:331–8. Demonstrates both similar and differential effects of chronic baroreflex activation and renal denervation on arterial pressure, neurohormonal responses, renal function, and heart rate in dogs with obesity-induced hypertension.PubMedCrossRefGoogle Scholar
  22. 22.
    Armitage JA, Burke SL, Prior LJ, et al. Rapid onset of renal sympathetic nerve activation in rabbits fed a high-fat diet. Hypertension. 2012;60:163–71.PubMedCrossRefGoogle Scholar
  23. 23.
    Schlaich MP, Sobotka PA, Krum, et al. Renal sympathetic-nerve ablation for uncontrolled hypertension. N Engl J Med. 2009;361:932–4.PubMedCrossRefGoogle Scholar
  24. 24.
    Tomaszewski M, Charchar, Maric C. Glomerular hyperfiltration: a new marker of metabolic risk. Kidney Int. 2007;71:816–21.PubMedCrossRefGoogle Scholar
  25. 25.
    • Lambert E, Sari CI, Daywood T, et al. Sympathetic Nervous System Activity is associated with obesity-induced subclinical organ damage in young adults. Hypertension. 2010;56:351–8. This study provides early evidence for glomerular hyperfiltration, a precursor of kidney disease, in parallel with increases in systolic blood pressure and muscle sympathetic nerve activity in overweight/obese college students when compared to their lean counterparts.PubMedCrossRefGoogle Scholar
  26. 26.
    Iliescu R, Irwin ED, Georgakopoulos D, Lohmeier TE. Renal responses to chronic suppression of central sympathetic outflow. Hypertension. 2012;60:749–56.PubMedCrossRefGoogle Scholar
  27. 27.
    Mahfoud F, Cremers B, Link B, et al. Renal hemodynamics and renal function after catheter-based sympathetic denervation in patients with resistant hypertension. Hypertension. 2012;60:419–24.PubMedCrossRefGoogle Scholar
  28. 28.
    Hering D, Mahfoud F, Walton AS, et al. Renal denervation in moderate to severe CKD. J Am Soc Nephrol. 2012;23:1250–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Alnima T, de Leeuw PW, Tan ES, Kroon AA. Renal responses to long-term carotid baroreflex activation therapy in patients with drug-resistant hypertension. Hypertension 2013, In press.Google Scholar
  30. 30.
    Poirier P, Giles TD, Bray GA, et al. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation. 2006;113:898–918.PubMedCrossRefGoogle Scholar
  31. 31.
    Wang TJ, Parise H, Levy D, et al. Obesity and the risk of new-onset atrial fibrillation. J Am Med Assoc. 2004;292:2471–7.CrossRefGoogle Scholar
  32. 32.
    Pietrasik G, Goldenberg I, McNitt S, et al. Obesity as a risk factor for sustained ventricular tachyarrhythmias in MADIT II patients. J Cardiovasc Electrophysiol. 2007;18:181–4.PubMedCrossRefGoogle Scholar
  33. 33.
    Wanahita N, Messerli FH, Bangalore S, et al. Atrial fibrillation and obesity—results of meta-analysis. Am Heart J. 2008;155:310–5.PubMedCrossRefGoogle Scholar
  34. 34.
    Tu W, Eckert GJ, DiMeglio LA, et al. Intensified effect of adiposity on blood pressure on overweight and obese children. Hypertension. 2011;58:818–24.PubMedCrossRefGoogle Scholar
  35. 35.
    Van Vliet BN, Hall JE, Mizelle HL, et al. Reduced parasympathetic control of heart rate in obese dogs. Am J Physiol Heart Circ Physiol. 1995;269:H629–37.Google Scholar
  36. 36.
    Aronne LJ, Mackintosh R, Rosenbaum M, et al. Autonomic nervous system activity in weight gain and weight loss. Am J Physiol Regul Integr Comp Physiol. 1995;269:R222–5.Google Scholar
  37. 37.
    Truett AA, Borne AT, Poincot MA, West DB. Autonomic control of blood pressure and heart rate in obese hypertensive dogs. Am J Physiol Regul Integr Comp Physiol. 1996;270:R541–9.Google Scholar
  38. 38.
    Tsuji H, Venditti Jr FJ, Manders ES, et al. Reduced heart rate variability and mortality risk in an elderly cohort. The Framingham Heart Study. Circulation. 1994;90:878–83.PubMedCrossRefGoogle Scholar
  39. 39.
    Tsuji H, Larson MG, Venditti FJ, et al. Impact of reduced heart rate variability on risk for cardiac events. The Framingham Heart Study. Circulation. 1996;94:2850–5.PubMedCrossRefGoogle Scholar
  40. 40.
    Reed MJ, Robertson CE, Addison PS. Heart rate variability measurements and the prediction of ventricular arrhythmias. QJM. 2005;98:87–95.PubMedCrossRefGoogle Scholar
  41. 41.
    Billman GE. Heart rate variability – a historical perspective. Front Physiol. 2011;2:1–13.CrossRefGoogle Scholar
  42. 42.
    Schwartz PJ, De Ferrari GM. Sympathetic-parasympathetic interaction in health and disease: abnormalities and relevance in heart failure. Heart Fail Rev. 2011;16:101–7.PubMedCrossRefGoogle Scholar
  43. 43.
    Grassi G, Seravalle G, Dell’Oro R, et al. Adrenergic and reflex abnormalities in obesity-related hypertension. Hypertension. 2000;36:538–42.PubMedCrossRefGoogle Scholar
  44. 44.
    Beske S, Alvarez GE, Ballard TP, Davy KP. Reduced cardiovagal baroreflex gain in visceral obesity: implications for the metabolic syndrome. Am J Physiol Heart Circ Physiol. 2002;282:H630–5.PubMedGoogle Scholar
  45. 45.
    Skrapari I, Tentolouris T, Perrea D, et al. Baroreflex sensitivity in obesity: relationship with cardiac autonomic nervous system activity. Obesity. 2007;15:1685–93.PubMedCrossRefGoogle Scholar
  46. 46.
    • Grassi G, Seravalle G, Quarti-Trevano F, et al. Reinforcement of the adrenergic overdrive in the metabolic syndrome complicated by obstructive sleep apnea. J Hypertens. 2010;28:1313–20. Measurements of muscle sympathetic nerve activity show that the sympathetic activation of metabolic syndrome occurs independently of obstructive sleep apnea (OSA) but that OSA has sustained effects to potentiate the sympathoexcitation.PubMedGoogle Scholar
  47. 47.
    Iliescu R, Tudorancea E, Irwin E, Lohmeier TE. Chronic baroreflex activation improves baroreflex control of heart rate in obesity. Hypertension. 2012;60:A477.CrossRefGoogle Scholar
  48. 48.
    Shankar A, Xiao J. Positive relationship between plasma leptin level and hypertension. Hypertension. 2010;56:623–8.PubMedCrossRefGoogle Scholar
  49. 49.
    Mark AL, Shaffer RA, Correia MLG, et al. Contrasting blood pressure effects of obesity in leptin-deficient ob/ob mice and agouti yellow obese mice. J Hypertens. 1999;17:1949–53.PubMedCrossRefGoogle Scholar
  50. 50.
    • Lim K, Burke SL, Head GA. Obesity-related hypertension and the role of insulin and leptin in high-fat-fed rabbits. Hypertension. 2013;61:628–34. Demonstrates that the central actions of endogenous leptin stimulate renal sympathetic nerve activity in conscious, obese hypertensive rabbits.PubMedCrossRefGoogle Scholar
  51. 51.
    Eikelis N, Schlaich M, Aggarwal A, et al. Interactions between leptin and the human sympathetic nervous system. Hypertension. 2003;41:1072–9.PubMedCrossRefGoogle Scholar
  52. 52.
    Wolk R, Abu SM. Shamsuzzaman, Somers VK. Obesity, sleep apnea, and Hypertension. Hypertension. 2003;42:1067–74.PubMedCrossRefGoogle Scholar
  53. 53.
    Witkowski A, Prejbisz A, Florczak E. Effects of renal sympathetic denervation on blood pressure, sleep apnea course, and glycemic control in patients with resistant hypertension and sleep apnea. Hypertension. 2011;58:559–65.PubMedCrossRefGoogle Scholar
  54. 54.
    Friedman O, Bradley TD, Chan CT, et al. Relationship between overnight rostral fluid shift and obstructive sleep apnea in drug-resistant hypertension. Hypertension. 2010;56:1077–82.PubMedCrossRefGoogle Scholar
  55. 55.
    Huber DA, Schreihofer AM. Attenuated baroreflex control of sympathetic nerve activity in obese Zucker rats by central mechanisms. J Physiol. 2010;588(9):1515–25.PubMedCrossRefGoogle Scholar
  56. 56.
    McCully BH, Brooks VL, Andresen MC. Diet-induced obesity severly impairs myelinated aortic baroreceptor reflex responses. Am J Physiol Heart Circ Physiol. 2012;302:H2083–91.PubMedCrossRefGoogle Scholar
  57. 57.
    Lohmeier TE, Warren S, Cunningham JT. Sustained activation of the central baroreceptor pathway in obesity hypertension. Hypertension. 2003;42:96–102.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Physiology and BiophysicsUniversity of Mississippi Medical CenterJacksonUSA
  2. 2.Department of PhysiologyUniversity of Medicine and Pharmacology “Gr. T. Popa” IasiIasiRomania

Personalised recommendations