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(Hypertension. 2001;37:663.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Central Leptin Infusion Attenuates the Cardiovascular and Metabolic Effects of Fasting in Rats

James Michael Overton; Todd Dennis Williams; James Bradley Chambers; Michael Edward Rashotte

From the Departments of Nutrition, Food, and Exercise Sciences (J.M.O., T.D.W.) and Psychology (J.B.C., M.E.R.), The Program in Neuroscience, Florida State University, Tallahassee.

Correspondence to J. Michael Overton, PhD, Department of Nutrition, Food, and Exercise Sciences and Program in Neuroscience, 236 Biomedical Research Facility, Florida State University, Tallahassee, FL 32306-4340. E-mail moverton{at}mailer.fsu.edu

The role of reduced leptin signaling in the regulation of cardiovascular responses to negative energy balance is not known. We tested the hypothesis that central infusion of leptin would attenuate the cardiovascular and metabolic responses to fasting. Male Sprague-Dawley rats, instrumented with telemetry devices and intracerebroventricular cannulas, were housed in metabolic chambers for continuous (24 hours) measurement of dark-phase (active) and light-phase (inactive) mean arterial pressure, heart rate, oxygen consumption, and respiratory quotient. Rats received central infusions of either saline (0.5 µL/h) or leptin (42 ng/h) for 6 days through osmotic pumps and were either fed ad libitum or were fasted for 48 hours followed by refeeding for 4 days. In ad lib animals, continuous intracerebroventricular leptin infusion significantly reduced caloric intake, body weight, and respiratory quotient compared with saline controls while having no effect on mean arterial pressure or heart rate. Fasting reduced mean arterial pressure, heart rate, oxygen consumption, and respiratory quotient in rats receiving saline infusions. Fasting-induced reductions in mean arterial pressure were specific to the active phase and were not attenuated by central leptin infusion. In contrast, intracerebroventricular leptin, at a dose that had no cardiovascular effects in ad lib control animals, completely prevented fasting-induced decreases in light-phase heart rate and oxygen consumption and blunted fasting-induced reductions in dark-phase heart rate and oxygen consumption. The results are consistent with the hypothesis that reductions in central leptin signaling contribute to the integrated cardiovascular and metabolic responses to acute caloric deprivation.

Key Words: diet • rats • neuroregulators • metabolism

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