We determined the central interactions of neuropeptide Y and leptin on cardiovascular and sympathetic responses in conscious rabbits. Intracerebroventricular injections of neuropeptide Y (0.1 and 1 nmol/40 microL) elicited dose-related decreases in arterial pressure and renal sympathetic nerve activity without a significant change in heart rate. Peak depressor or sympathoinhibitory responses of mean arterial pressure and renal sympathetic nerve activity (-13.0+/-1.5 mm Hg and -27.6+/-4.9%) were observed at 25 and 20 minutes after intracerebroventricular injection of 1 nmol of neuropeptide Y, respectively. Pretreatment with intracerebroventricular injection of leptin (3 nmol) prevented the depressor and sympathoinhibitory responses elicited by intracerebroventricular neuropeptide Y. Intravenous injection of the same dose of neuropeptide Y (1 nmol) as that used in the intracerebroventricular experiment failed to cause any cardiovascular and renal sympathetic nerve responses. On the other hand, a subdepressor dose of intracerebroventricular infusion of neuropeptide Y (1 nmol/300 microL per hour) significantly attenuated the baroreflex sensitivities assessed by renal sympathetic nerve activity and heart rate compared with vehicle infusion (G(max); -7.4+/-0.7 versus -13.7+/-0.9%/mm Hg, P:<0.01, and -4.0+/-0.3 versus -6.7+/-0.8 bpm/mm Hg, P:<0.05, respectively). These results suggest that central neuropeptide Y participates in the regulations of the sympathetic nerve activity to kidney and the baroreceptor reflex and that the depressor response induced by intracerebroventricular neuropeptide Y is modulated, at least in part, by central leptin in conscious rabbits.
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