on March 31, 2003
Published online before print March 31, 2003, doi: 10.1161/01.HYP.0000066289.17754.49
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Submitted on October 30, 2002
From the Baker Heart Research Institute and Alfred Baker Medical Unit, Alfred Hospital, Melbourne, Australia. * To whom correspondence should be addressed. E-mail: murray.esler{at}baker.edu.au.
Abstract--Results from animal experimentation suggest a 2-way interaction between leptin and the sympathetic nervous system, with leptin causing sympathetic activation and conversely, with the sympathetic system exercising regulatory feedback inhibition over leptin release. We have now tested this hypothesis in humans. In the absence of results from leptin infusions, to test for sympathetic stimulation of leptin release, we sought a quantitative naturalistic linkage of sympathetic activity with leptin plasma concentration across a broad range of leptin values in men of widely differing adiposity. Renal norepinephrine spillover was correlated with plasma leptin (r=0.628, P<0.01), but other measures of sympathoadrenal function did not. To test for sympathetic and adrenomedullary inhibition of leptin release, we studied clinical models of high sympathetic tone, heart failure, and essential hypertension, in which lowered plasma leptin levels might have been expected but were not found; a model of low sympathetic activity, pure autonomic failure, in which plasma leptin level was normal (6.1±1.2 vs 12.8±3.1 ng/mL in healthy subjects); and a clinical model of reduced epinephrine secretion, healthy aging, in which plasma leptin level again was normal (5.7±1.1 ng/mL vs 4.0±0.9 ng/mL in men >60 years and <35 years, respectively). Paradoxically, leptin concentration was elevated in heart failure, caused entirely by reduced renal clearance of leptin release, 142.0±30.5 mL/min, compared with 56.9±18.9 mL/min (P<0.05). These results provide some support for the view that leptin stimulates the sympathetic nervous system, at least for renal sympathetic outflow, but do not confirm the concept of regulatory feedback inhibition of leptin release by the sympathetic nervous system.
Revised on November 13, 2002
Interactions Between Leptin and the Human Sympathetic Nervous System
Nina Eikelis;
Key words: leptin • nervous system, sympathetic renal • heart failure • hypertension, essential • autonomic nervous system • aging • obesity
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