Current Hypertension Reports

, Volume 6, Issue 3, pp 236–240 | Cite as

Leptin, sympathetic nervous system, and baroreflex function

  • Guido Grassi


In addition to its direct effects on energy metabolism and caloric intake, leptin exerts several circulatory effects that appear to be mediated by an interaction with the sympathetic nervous system and the major reflexogenic area involved in cardiovascular homeostatic control—that is, the arterial baroreflex. In this paper, the relationships between the adipocyte hormone and the neuroadrenergic function are reviewed, taking into account data collected in experimental animal models as well as in human cardiovascular (hypertension and heart failure) and noncardiovascular (obesity) diseases that are characterized by a hyperadrenergic state coupled with a hyperleptinemia.


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References and Recommended Reading

  1. 1.
    Flier JS: What’s in a name? In search of leptin’s physiologic role. J Clin Endocrinol Metab 1998, 83:1407–1413.PubMedCrossRefGoogle Scholar
  2. 2.
    Hall JE, Shek EW, Brands MW: Is leptin a link between obesity and hypertension? Curr Opin Endocrinol Diabetes 1999, 6:225–229.CrossRefGoogle Scholar
  3. 3.
    Ahima RS, Flier JS: Leptin. Annu Rev Physiol 2000, 62:413–437.PubMedCrossRefGoogle Scholar
  4. 4.
    Soderberg S, Ahren B, Jansson JH, et al.: Leptin is associated with increased risk of myocardial infarction. J Intern Med 1999, 246:409–418.PubMedCrossRefGoogle Scholar
  5. 5.
    Haynes WG, Sivitz WI, Morgan DA, et al.: Sympathetic and cardiorenal actions of leptin. Hypertension 1997, 30:619–623. This study represents one of the first demonstrations of the regional effects of leptin on the sympathetic nervous system in experimental animals.PubMedGoogle Scholar
  6. 6.
    Lembo G, Vecchione C, Fratta L, et al.: Leptin induces direct vasodilation through distinct endothelial mechanisms. Diabetes 2000, 49:293–297.PubMedCrossRefGoogle Scholar
  7. 7.
    Kuo J, Jones OB, Hall JE: Inhibition of NO synthesis enhances chronic cardiovascular and renal actions of leptin. Hypertension 2001, 37:670–676.PubMedGoogle Scholar
  8. 8.
    Rayner DV, Trayhurn P: Regulation of leptin production: sympathetic nervous system interactions. J Mol Med 2001, 79:8–20.PubMedCrossRefGoogle Scholar
  9. 9.
    Trayhurn P, Duncan JS, Hoggard N, Rayner DV: Regulation of leptin production: A dominant role for the sympathetic nervous system? Proc Nutr Soc 1998, 57:413–419.PubMedCrossRefGoogle Scholar
  10. 10.
    Haynes WG: Interaction between leptin and sympathetic nervous system in hypertension. Curr Hypertens Rep 2000, 2:311–318.PubMedCrossRefGoogle Scholar
  11. 11.
    Hall JH, Hildebrandt DA, Kuo J: Obesity hypertension: role of leptin and sympathetic nervous system. Am J Hypertens 2001, 14:103S-115S. A complete and comprehensive review linking the obese state to hypertension development throughout metabolic and adrenergic mechanisms.PubMedCrossRefGoogle Scholar
  12. 12.
    Shek EW, Brands MW, Hall JE: Chronic leptin infusion increases arterial pressure. Hypertension 1998, 31:409–414.PubMedGoogle Scholar
  13. 13.
    Shek EW, Kim PK, Hall JE: Adrenergic blockade prevents leptin-induced hypertension [abstract]. FASEB J 1999, 13:A456.Google Scholar
  14. 14.
    Haynes WG, Morgan DA, Djalali A, et al.: Interactions between the melanocortin system and leptin in control of sympathetic nerve traffic. Hypertension 1999, 33:542–547.PubMedGoogle Scholar
  15. 15.
    Huszar D, Lynch CA, Firechild-Huntress V, et al.: Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 1997, 88:131–141.PubMedCrossRefGoogle Scholar
  16. 16.
    El-Haschimi K, Pierroz DD, Hileman SM, et al.: Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity. J Clin Invest 2000, 105:1827–1832.PubMedGoogle Scholar
  17. 17.
    Matsumura K, Abe I, Tsuchihashi T, Fujishima M: Central effects of leptin on cardiovascular and neurohormonal responses in conscious rabbits. Am J Physiol 2000, 278:R1314-R1320.Google Scholar
  18. 18.
    Hausberg M, Morgan DA, Chapleau MA, et al.: Differential modulation of leptin-induced sympathoexcitation by baroreflex activation. J Hypertens 2002, 20:1633–1641. The study, performed in experimental animals, provides data on the modifications of the baroreflex function induced by leptin.PubMedCrossRefGoogle Scholar
  19. 19.
    Grassi G, Esler M: How to assess sympathetic activity in humans. J Hypertens 1999, 17:719–734. This review is focused on the pros and cons of the various methodologic approaches used to quantify adrenergic activity in man.PubMedCrossRefGoogle Scholar
  20. 20.
    Esler M, Jennings G, Lambert G, et al.: Overflow of catecholamine neurotransmitters to the circulation: source, fate, and functions. Physiol Rev 1990, 70:963–986.PubMedGoogle Scholar
  21. 21.
    Thomas JA, Marks BH: Plasma norepinephrine in congestive heart failure. Am J Cardiol 1978, 41:233–238.PubMedCrossRefGoogle Scholar
  22. 22.
    Grassi G: Role of the sympathetic nervous system in human hypertension. J Hypertens 1998, 16:1979–1987.PubMedCrossRefGoogle Scholar
  23. 23.
    Grassi G, Colombo M, Seravalle G, et al.: Dissociation between muscle and skin sympathetic nerve activity in essential hypertension, obesity and congestive heart failure. Hypertension 1998, 31:64–67.PubMedGoogle Scholar
  24. 24.
    Esler M, Kaye D: Sympathetic nervous system activation in essential hypertension, cardiac failure and psychosomatic heart disease. J Cardiovasc Pharmacol 2000, 35:51–57.CrossRefGoogle Scholar
  25. 25.
    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.PubMedGoogle Scholar
  26. 26.
    Grassi G, Cattaneo B, Seravalle G, et al.: Baroreflex control of sympathetic activity in essential and secondary hypertension. Hypertension 1998, 31:68–72.PubMedGoogle Scholar
  27. 27.
    Grassi G, Seravalle G, Cattaneo BM, et al.: Sympathetic activation and loss of reflex control in mild congestive heart failure. Circulation 1995, 92:3206–3211.PubMedGoogle Scholar
  28. 28.
    Scherrer U, Randin D, Tappy L, et al.: Body fat and sympathetic nerve activity in healthy subjects. Circulation 1994, 89:2634–2640.PubMedGoogle Scholar
  29. 29.
    Dell’Oro R, Seravalle G, Quarti Trevano F, et al.: Relationship between sympathetic activation, baroreflex disfunction and gender-related body fat distribution in obesity. J Hypertens 2001, 19(Suppl 2):S102.Google Scholar
  30. 30.
    Grassi G, Seravalle G, Cattaneo BM, et al.: Sympathetic activation in obese normotensive subjects. Hypertension 1995, 25:560–563.PubMedGoogle Scholar
  31. 31.
    Mancia G, Grassi G, Giannattasio C, Seravalle G: Sympathetic activation in the pathogenesis of hypertension and progression of organ damage. Hypertension 1999, 34:724–728.PubMedGoogle Scholar
  32. 32.
    Cohn JN, Levine TB, Olivari MT, et al.: Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med 1984, 311:819–823.PubMedCrossRefGoogle Scholar
  33. 33.
    Grassi G: Sympathetic deactivation as a goal of nonpharmacological and pharmacological antihypertensive treatment: rationale and options. Curr Hyperten Rep 2003, 5:277–280.Google Scholar
  34. 34.
    Makintosh RM, Hirsch J: The effects of leptin administration in non-obese human subjects. Obes Res 2001, 9:462–469.CrossRefGoogle Scholar
  35. 35.
    Narkiewicz K, Kato M, Phillips BG, et al.: Leptin interacts with heart rate but not sympathetic nerve traffic in healthy male subjects. J Hypertens 2001, 19:1089–1094. One of the first reports on the relationships between the adipocyte hormone and the sympathetic nervous system in man.PubMedCrossRefGoogle Scholar
  36. 36.
    Grassi G, Vailati S, Bertinieri G, et al.: Heart rate as a marker of sympathetic activity. J Hypertens 1998, 16:1635–1639.PubMedCrossRefGoogle Scholar
  37. 37.
    Snitker S, Pratley RE, Nicolson M, et al.: Relation between muscle sympathetic nerve activity and plasma leptin concentration. Obese Res 1997, 5:338–340.Google Scholar
  38. 38.
    Paolisso G, Manzella D, Montano N, et al.: Plasma leptin concentrations and cardiac autonomic nervous system in healthy subjects with different body weights. J Clin Endocrinol Metab 2000, 85:1910–1814.Google Scholar
  39. 39.
    Tank J, Jordan J, Diedrick A, et al.: Bound leptin and sympathetic outflow in non-obese men. J Clin Endocrinol Metab 2003, 88:4955–4959. The study provides information on the relative importance of free versus bound leptin in the relationship with adrenergic function.PubMedCrossRefGoogle Scholar
  40. 40.
    Eikelis N, Schlaich M, Aggarwal A, et al.: Interactions between leptin and the human sympathetic nervous system. Hypertension 2003, 41:1072–1079. A report clarifying the behavior of regional sympathetic activity and leptin in different cardiovascular or noncardiovascular diseases.PubMedCrossRefGoogle Scholar
  41. 41.
    Phillips BG, Kato M, Narkiewicz K, et al.: Increases in leptin levels, sympathetic drive and weight gain in obstructive sleep apnea. Am J Physiol 2000, 279:H234-H237.Google Scholar

Copyright information

© Current Science Inc 2004

Authors and Affiliations

  • Guido Grassi
    • 1
  1. 1.Clinica Medica, Ospedale San GerardoMonzaItaly

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