Central Ghrelin Modulates Sympathetic Activity in Conscious Rabbits

Abstract

Ghrelin is an orexigenic peptide originally isolated from the stomach. Intravenous administration of ghrelin has been shown to elicit a decrease in arterial pressure without a significant change in heart rate (HR), suggesting that ghrelin may act on the central nervous system to modulate sympathetic activity. The aim of the present study was to determine the central effects of ghrelin on cardiovascular and sympathetic responses in conscious rabbits. Intravenous injection of ghrelin elicited dose-related decreases in arterial pressure and HR, without a significant change in renal sympathetic nerve activity. On the other hand, intracerebroventricular injection of 1 nmol of ghrelin decreased arterial pressure, HR, and renal sympathetic nerve activity. Peak depressor or sympathoinhibitory responses of mean arterial pressure and renal sympathetic nerve activity (−19.0±1.5 mm Hg and −43.3±5.4%) were observed at 50 and 40 minutes, respectively, after intracerebroventricular injection of 1 nmol of ghrelin. Furthermore, a subdepressor dose of intracerebroventricular infusion of ghrelin (0.3 nmol/150 μL per hour) significantly augmented the baroreflex sensitivities assessed by renal sympathetic nerve activity and HR compared with those of vehicle infusion (G max ; −17.8±3.1 versus −9.4±1.6%/mm Hg, P <0.05; −12.5±1.8 versus −6.6±1.2 bpm/mm Hg, P <0.05; respectively). These results suggest that intravenous injection of ghrelin acts, at least in part, on the central nervous system to decrease arterial pressure and renal sympathetic nerve activity, and that central ghrelin participates in the regulations of the sympathetic nerve activity to the kidney and the baroreceptor reflex in conscious rabbits.