Skip to main content

Advertisement

SpringerLink
Log in

Mediators of sympathetic activation in metabolic syndrome obesity

  • Published:
Current Hypertension Reports Aims and scope Submit manuscript

Abstract

The metabolic syndrome represents a major public health burden because of its high prevalence in the general population and its association with cardiovascular disease and type 2 diabetes. Accumulated evidence based on biochemical, neurophysiologic, and indirect measurements of autonomic activity indicate that visceral obesity and the metabolic syndrome are associated with enhanced sympathetic neural drive and vagal impairment. The mechanisms linking metabolic syndrome with sympathetic activation are complex and not completely understood, and cause-effect relationships need further clarification from prospective trials. Components of the metabolic syndrome that may directly or indirectly enhance sympathetic drive include hyperinsulinemia, leptin, nonesterified fatty acids, proinflammatory cytokines, angiotensinogen, baroreflex impairment, and obstructive sleep apnea. β-Adrenoceptor polymorphisms have also been associated with adrenoceptor desensitization, increased adiposity, insulin resistance, and enhanced sympathetic activity. Because chronic sympathetic activation contributes to hypertension and its target-organ damage, sympatho-inhibition remains an important goal in the therapeutic management of the metabolic syndrome.

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.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Cameron AJ, Magliano DJ, Zimmet PZ, et al.: The metabolic syndrome in Australia: prevalence using four definitions. Diabetes Res Clin Pract 2007, 77: 471–478.

    Article  PubMed  Google Scholar 

  2. Grassi G, Esler M: How to assess sympathetic activity in humans. J Hypertens 1999, 17: 719–734.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  4. Kingwell BA, Thompson JM, Kaye DM, et al.: Heart rate spectral analysis, cardiac norepinephrine spillover, and muscle sympathetic nerve activity during human sympathetic nervous activation and failure. Circulation 1994, 90:234–240.

    PubMed  CAS  Google Scholar 

  5. Brunner EJ, Hemmingway H, Walker BR, et al.: Adrenocortical, autonomic, and inflammatory causes of the metabolic syndrome. Nested case-control study. Circulation 2002, 106: 2659–2665.

    Article  PubMed  CAS  Google Scholar 

  6. Lee ZSK, Critchley JAH, Tomlinson B, et al.: Urinary epinephrine and norepinephrine interrelations with obesity, insulin, and the metabolic syndrome in Hong Kong Chinese. Metabolism 2001; 50: 135–143.

    Article  PubMed  CAS  Google Scholar 

  7. Huggett RJ, Burns J, MacKintosh AF, Mary DA: Sympathetic neural activation in nondiabetic metabolic syndrome and its further augmentation by hypertension. Hypertension 2004, 44: 847–852.

    Article  PubMed  CAS  Google Scholar 

  8. Grassi G, Dell’Oro R, Quatri-Trevano F, et al.: Neuroadrenergic and reflex abnormalities in patients with metabolic syndrome. Diabetologia 2005, 48: 1359–1365.

    Article  PubMed  CAS  Google Scholar 

  9. Alvarez GE, Beske SD, Ballard TP, Davy KP: Sympathetic neural activation in visceral obesity. Circulation 2002, 106: 2533–2536.

    Article  PubMed  Google Scholar 

  10. Grassi G, Dell’Oro R, Facchini A, et al.: Effect of central and peripheral body fat distribution on sympathetic and baroreflex function in obese normotensives. J Hypertens 2004, 22: 2363–2369.

    Article  PubMed  CAS  Google Scholar 

  11. Vaz M, Jennings G, Turner A, et al.: Regional sympathetic nervous activity and oxygen consumption in obese normotensive human subjects. Circulation 1997, 96: 3423–3429.

    PubMed  CAS  Google Scholar 

  12. Rumantir M, Vaz M, Jennings GL, et al.: Neural mechanisms in human obesity-related hypertension. J Hypertens 1999, 17: 1125–1133.

    Article  PubMed  CAS  Google Scholar 

  13. Straznicky N, Lambert E, Lambert G, et al.: Effects of dietary weight loss on sympathetic activity and cardiac risk factors associated with the metabolic syndrome. J Clin Endocrinol Metab 2005, 90: 5998–6005.

    Article  PubMed  CAS  Google Scholar 

  14. Poehlman ET, Danforth E: Endurance training increases resting metabolic rate and norepinephrine appearance rate in older individuals. Am J Physiol 1991, 261: E233–E239.

    PubMed  CAS  Google Scholar 

  15. Poehlman ET, Gardner AW, Goran MI, et al.: Sympathetic nervous system activity, body fatness and body fat distribution in younger and older males. J Appl Physiol 1995, 78: 802–806.

    PubMed  CAS  Google Scholar 

  16. Stein PK, Barzilay JI, Domitrovich PP, et al.: The relationship of heart rate and heart rate variability to non-diabetic fasting glucose levels and the metabolic syndrome: the Cardiovascular Health Study. Diabetic Med 2007, 24: 855–863.

    Article  PubMed  CAS  Google Scholar 

  17. Sung J, Choi Y, Park JB.: Metabolic syndrome is associated with delayed heart rate recovery after exercise. J Korean Med Sci 2006, 21: 621–626.

    Article  PubMed  Google Scholar 

  18. Weyer C, Pratley RE, Snitker S, et al.: Ethnic differences in insulinemia and sympathetic tone as links between obesity and blood pressure. Hypertension 2000, 36: 531–537.

    PubMed  CAS  Google Scholar 

  19. Lambert E, Straznicky N, Eikelis N, et al.: Gender differences in sympathetic nervous activity: influence of body mass and blood pressure. J Hypertens 2007, 25: 1411–1419.

    Article  PubMed  CAS  Google Scholar 

  20. Jones PP, Snitker S, Skinner JS, Ravussin E.: Gender differences in muscle sympathetic nerve activity: effect of body fat distribution. Am J Physiol 1996, 270: E363–E366.

    PubMed  CAS  Google Scholar 

  21. Abate N, Mansour Y, Tuncle M, et al.: Overweight and sympathetic overactivity in Black Americans. Hypertension 2001, 38: 379–383.

    PubMed  CAS  Google Scholar 

  22. Landsberg L: Diet, obesity and hypertension: an hypothesis involving insulin, the sympathetic nervous system, and adaptive thermogenesis. Q J Med 1986, 236: 1081–1090.

    Google Scholar 

  23. Reaven G: Banting Lecture 1988. Role of insulin resistance in human disease. Diabetes 1988, 37: 1595–1607.

    Article  PubMed  CAS  Google Scholar 

  24. Grundy SM: What is the contribution of obesity to the metabolic syndrome? Endocrinol Metab Clin N Am 2004, 33: 267–282.

    Article  Google Scholar 

  25. Julius S, Valentini M, Palatini P: Overweight and hypertension: a 2-way street? Hypertension 2000, 35: 807–813.

    PubMed  CAS  Google Scholar 

  26. Masuo K, Kawaguchi H, Mikami H, et al.: Serum uric acid and plasma norepinephrine concentrations predict subsequent weight gain and blood pressure elevation. Hypertension 2003, 42: 474–480.

    Article  PubMed  CAS  Google Scholar 

  27. Gudmundsdottir H, Strand A, Kjeldsen S, et al.: Arterial noradrenaline predicts rise in body mass index in a 20-year follow-up of lean normotensive and hypertensive men [abstract]. J Hypertens 2008, 26(Suppl): S347.

    Google Scholar 

  28. Scherrer U, Sartori C: Insulin as a vascular and sympathoexcitatory hormone. Circulation 1997, 96: 4104–4113.

    PubMed  CAS  Google Scholar 

  29. Vollenweider P, Randin D, Tappy L, et al.: Impaired insulininduced sympathetic neural activation and vasodilation in skeletal muscle in obese humans. J Clin Invest 1994; 93: 2365–2371.

    Article  PubMed  CAS  Google Scholar 

  30. Straznicky N, Masuo K, Lambert G, et al.: Blunted sympathetic neural response to oral glucose in insulin resistant metabolic syndrome subjects [abstract]. J Hypertens 2008, 26:S350.

    Google Scholar 

  31. Kaiyala KJ, Prigeon RL, Kahn SE, et al.: Obesity induced by a high-fat diet is associated with reduced brain insulin transport in dogs. Diabetes 2000, 49:1525–1533.

    Article  PubMed  CAS  Google Scholar 

  32. Frontoni S, Bracaglia D, Baroni A, et al.: Early dysfunction in glucose-tolerant but insulin-resistant offspring of type 2 diabetic patients. Hypertension 2003, 41:1223–1227.

    Article  PubMed  CAS  Google Scholar 

  33. Watanabe K, Komatsu J, Kurata M, et al.: Improvement of insulin resistance by troglitazone ameliorates cardiac sympathetic nervous dysfunction in patients with essential hypertension. J Hypertens 2004, 22:1761–1768.

    Article  PubMed  CAS  Google Scholar 

  34. Jamerson KA, Julius S, Gudbrandsson T, et al.: Reflex sympathetic activation induces acute insulin resistance in the human forearm. Hypertension 1993, 21:618–623.

    PubMed  CAS  Google Scholar 

  35. Van Baak MA: The peripheral sympathetic nervous system in human obesity. Obes Rev 2001, 2:3–14.

    Article  PubMed  Google Scholar 

  36. Reynisdottir S, Ellerfeldt K, Wahrenberg H, et al.: Multiple lipolysis defects in the insulin resistance (metabolic) syndrome. J Clin Invest 1994, 93:2590–2599.

    Article  PubMed  CAS  Google Scholar 

  37. Masuo K, Katsuya T, Fu Y, et al.: β 2-adrenoceptor polymorphisms relate to insulin resistance and sympathetic overactivity as early markers of metabolic disease in nonobese, normotensive individuals. Am J Hypertens 2005, 18:1009–1014.

    Article  PubMed  CAS  Google Scholar 

  38. Lindgren K, Hagelin E, Hansen N, Lind L: Baroreceptor sensitivity is impaired in elderly subjects with metabolic syndrome and insulin resistance. J Hypertens 2006, 24:143–150.

    Article  PubMed  CAS  Google Scholar 

  39. Lucini D, Cusumano G, Bellia A, et al.: Is reduced barore-flex gain a component of the metabolic syndrome? Insights from the LINOSA study. J Hypertens 2006, 24:361–370.

    Article  PubMed  CAS  Google Scholar 

  40. Grassi G, Facchini A, Trevano Q, et al.: Obstructive sleep apnea-dependent and-independent adrenergic activation in obesity. Hypertension 2005, 46:321–325.

    Article  PubMed  CAS  Google Scholar 

  41. Imadojemu VA, Mawji Z, Kunselman A, et al.: Sympathetic chemoreflex responses in obstructive sleep apnea and effects of continuous positive airway pressure therapy. Chest 2007, 131:1406–1413.

    Article  PubMed  Google Scholar 

  42. Noda A, Nakata S, Koike Y, et al.: Continuous positive airway pressure improves daytime baroreflex sensitivity and nitric oxide production in patients with moderate to severe obstructive sleep apnea syndrome. Hypertens Res 2007, 30:669–676.

    Article  PubMed  CAS  Google Scholar 

  43. Phillips CG, 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 apnea. J Sleep Res 2007, 16:217–225.

    Article  PubMed  Google Scholar 

  44. Eikelis N, Schlaich M, Aggarwal A, et al.: Interactions between leptin and the human sympathetic nervous system. Hypertension 2003, 41:1072–1079.

    Article  PubMed  CAS  Google Scholar 

  45. Alvarez G, Ballard TP, Beske SD, Davy KPD: Subcutaneous obesity is not associated with sympathetic neural activation. Am J Physiol Heart Circ Physiol 2004, 287:H414–H418.

    Article  PubMed  CAS  Google Scholar 

  46. Gadegbeku CA, Dhandayuthapani A, Sadler ZE, Egan BM: Raising lipids acutely reduces baroreflex sensitivity. Am J Hypertens 2002, 15:479–485.

    Article  PubMed  CAS  Google Scholar 

  47. Grekin RJ, Ngarmukos CO, Williams DM, Supiano MA: Renal norepinephrine spillover during infusion of nonesterified fatty acids. Am J Hypertens 2005, 18:422–426.

    Article  PubMed  CAS  Google Scholar 

  48. Grassi G, Seravalle G, Dell’Oro R, et al.: Comparative effects of candesartan and hydrochlorothiazide on blood pressure, insulin sensitivity, and sympathetic drive in obese hypertensive individuals: results of the CROSS study. J Hypertens 2003, 21:1761–1769.

    Article  PubMed  CAS  Google Scholar 

  49. Struck J, Muck P, Trubger D, et al.: Effects of selective angiotensin II receptor blockade on sympathetic nerve activity in primary hypertensive subjects. J Hypertens 2002, 20:1143–1149.

    Article  PubMed  CAS  Google Scholar 

  50. Wessel J, Moratorio G, Rao F, et al.: C-reactive protein, an ‘intermediate phenotype’ for inflammation: human twin studies reveal heritability, association with blood pressure and the metabolic syndrome, and the influence of common polymorphism at catecholaminergic/β-adrenergic pathway loci. J Hypertens 2007, 25:329–343.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes Institute, PO Box 6492, St. Kilda Road Central, Melbourne, Victoria, 8008, Australia

    Nora E. Straznicky

Authors
  1. Nora E. Straznicky
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nina Eikelis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elisabeth A. Lambert
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Murray D. Esler
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nora E. Straznicky.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Straznicky, N.E., Eikelis, N., Lambert, E.A. et al. Mediators of sympathetic activation in metabolic syndrome obesity. Current Science Inc 10, 440–447 (2008). https://doi.org/10.1007/s11906-008-0083-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11906-008-0083-1

Keywords

Search

Navigation