Published Online
on August 25, 2003

A more recent version of this article appeared on October 1, 2003

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Submitted on May 14, 2003
Revised on June 3, 2003

Cardiovascular Responses Evoked by Leptin Acting on Neurons in the Ventromedial and Dorsomedial Hypothalamus

Ainsley J. Marsh; Marco A.P. Fontes; Suzanne Killinger; Dorota B. Pawlak; Jaimie W. Polson; and Roger A.L. Dampney^*

From the Department of Physiology and Institute for Biomedical Research (A.J.M., M.A.P.F., S.K., J.W.P., R.A.L.D.) and the School of Molecular and Microbial Biosciences (D.B.P.), University of Sydney, Sydney, Australia.

^* To whom correspondence should be addressed. E-mail: rogerd{at}physiol.usyd.edu.au.

Abstract--Leptin, a circulating hormone produced by adipose tissue, is believed to act on the hypothalamus to increase sympathetic vasomotor activity, in addition to its well-known effects on appetite and energy expenditure. In this study, we determined the cardiovascular effects of direct application of leptin to specific cell groups within the hypothalamus that are known to be activated by circulating leptin. In rats anesthetized with urethane, microinjections of leptin (16 ng in 20 nL solution) were made into the ventromedial hypothalamic nucleus, dorsomedial hypothalamic nucleus, and paraventricular nucleus. Compared with vehicle solution, microinjections of leptin into the ventromedial hypothalamic nucleus evoked significant increases in arterial pressure and renal sympathetic nerve activity, but not heart rate. In contrast, microinjections of leptin into the dorsomedial hypothalamic nucleus evoked significant increases in arterial pressure and heart rate but not renal sympathetic nerve activity, whereas microinjections of leptin into the paraventricular nucleus had no significant effect on any of the measured cardiovascular variables. These results indicate that the ventromedial and dorsomedial hypothalamic regions might be important sites at which leptin activation leads to increases in sympathetic vasomotor activity and heart rate, as occurs in obesity-related hypertension.

Key words: hypothalamus • sympathetic nervous system • arterial pressure • heart rate • brain • hypertension, experimental • obesity

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