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Central effects of leptin on cardiovascular and neurohormonal responses in conscious rabbits.

We determined the cardiovascular and neurohormonal responses to intracerebroventricular injection of leptin in conscious rabbits. Intracerebroventricular injection of leptin elicited dose-related increases in mean arterial pressure and renal sympathetic nerve activity while producing no consistent, significant increases in heart rate. Peak values of mean arterial pressure and renal sympathetic nerve activity induced by intracerebroventricular injection of 50 microgram of leptin (+17.3 +/- 1.2 mmHg and +47.9 +/- 12.0%) were obtained at 10 and 20 min after injection, respectively. Plasma catecholamine concentrations significantly increased at 60 min after intracerebroventricular injection of leptin (control vs. 60 min; epinephrine: 33 +/- 12 vs. 97 +/- 27 pg/ml, P < 0.05; norepinephrine: 298 +/- 39 vs. 503 +/- 86 pg/ml, P < 0.05). Intracerebroventricular injection of leptin also caused significant increases in plasma vasopressin and glucose levels. However, pretreatment with intravenous injection of pentolinium (5 mg/kg), a ganglion blocking agent, abolished these cardiovascular and neurohormonal responses. On the other hand, intravenous injection of the same dose of leptin (50 microgram) as used in the intracerebroventricular experiment failed to cause any cardiovascular and renal sympathetic nerve responses. These results suggest that intracerebroventricular leptin acts in the central nervous system and activates sympathoadrenal outflow, resulting in increases in arterial pressure and plasma glucose levels in conscious rabbits.