Abstract
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.
Similar content being viewed by others
References and Recommended Reading
Flier JS: What’s in a name? In search of leptin’s physiologic role. J Clin Endocrinol Metab 1998, 83:1407–1413.
Hall JE, Shek EW, Brands MW: Is leptin a link between obesity and hypertension? Curr Opin Endocrinol Diabetes 1999, 6:225–229.
Ahima RS, Flier JS: Leptin. Annu Rev Physiol 2000, 62:413–437.
Soderberg S, Ahren B, Jansson JH, et al.: Leptin is associated with increased risk of myocardial infarction. J Intern Med 1999, 246:409–418.
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.
Lembo G, Vecchione C, Fratta L, et al.: Leptin induces direct vasodilation through distinct endothelial mechanisms. Diabetes 2000, 49:293–297.
Kuo J, Jones OB, Hall JE: Inhibition of NO synthesis enhances chronic cardiovascular and renal actions of leptin. Hypertension 2001, 37:670–676.
Rayner DV, Trayhurn P: Regulation of leptin production: sympathetic nervous system interactions. J Mol Med 2001, 79:8–20.
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.
Haynes WG: Interaction between leptin and sympathetic nervous system in hypertension. Curr Hypertens Rep 2000, 2:311–318.
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.
Shek EW, Brands MW, Hall JE: Chronic leptin infusion increases arterial pressure. Hypertension 1998, 31:409–414.
Shek EW, Kim PK, Hall JE: Adrenergic blockade prevents leptin-induced hypertension [abstract]. FASEB J 1999, 13:A456.
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.
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.
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.
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.
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.
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.
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.
Thomas JA, Marks BH: Plasma norepinephrine in congestive heart failure. Am J Cardiol 1978, 41:233–238.
Grassi G: Role of the sympathetic nervous system in human hypertension. J Hypertens 1998, 16:1979–1987.
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.
Esler M, Kaye D: Sympathetic nervous system activation in essential hypertension, cardiac failure and psychosomatic heart disease. J Cardiovasc Pharmacol 2000, 35:51–57.
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.
Grassi G, Cattaneo B, Seravalle G, et al.: Baroreflex control of sympathetic activity in essential and secondary hypertension. Hypertension 1998, 31:68–72.
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.
Scherrer U, Randin D, Tappy L, et al.: Body fat and sympathetic nerve activity in healthy subjects. Circulation 1994, 89:2634–2640.
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.
Grassi G, Seravalle G, Cattaneo BM, et al.: Sympathetic activation in obese normotensive subjects. Hypertension 1995, 25:560–563.
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.
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.
Grassi G: Sympathetic deactivation as a goal of nonpharmacological and pharmacological antihypertensive treatment: rationale and options. Curr Hyperten Rep 2003, 5:277–280.
Makintosh RM, Hirsch J: The effects of leptin administration in non-obese human subjects. Obes Res 2001, 9:462–469.
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.
Grassi G, Vailati S, Bertinieri G, et al.: Heart rate as a marker of sympathetic activity. J Hypertens 1998, 16:1635–1639.
Snitker S, Pratley RE, Nicolson M, et al.: Relation between muscle sympathetic nerve activity and plasma leptin concentration. Obese Res 1997, 5:338–340.
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.
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.
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.
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.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Grassi, G. Leptin, sympathetic nervous system, and baroreflex function. Current Science Inc 6, 236–240 (2004). https://doi.org/10.1007/s11906-004-0075-8
Issue Date:
DOI: https://doi.org/10.1007/s11906-004-0075-8