Abstract-Ghrelin is an orexigenic peptide originally isolated from the stomach. Intracerebroventricular administration of ghrelin has been shown to elicit decreases in arterial pressure and renal sympathetic nerve activity in conscious rabbits. The aim of the present study was to determine the role of ghrelin in the brain stem in cardiovascular responses in rats. Unilateral microinjection of ghrelin into the nucleus of the solitary tract significantly decreased the mean arterial pressure and heart rate (Ϫ17.3Ϯ0.8 mm Hg and Ϫ13.6Ϯ3.5 bpm by 20 pmol). The microinjection of ghrelin into the nucleus of the solitary tract also suppressed the renal sympathetic nerve activity (Ϫ29.5Ϯ3.4%; PϽ0.0001). Pretreatment with intravenous injection of pentolinium (5 mg/kg), a ganglion-blocking agent, eliminated these cardiovascular responses induced by the microinjection of ghrelin (20 pmol) into the nucleus of the solitary tract; however, pretreatment with intravenous injection of atropine sulfate (0.1 mg/kg), an antagonist of muscarinic acetylcholine receptors, failed to prevent them. In contrast, unilateral microinjection of ghrelin into the area postrema, rostral, and caudal ventrolateral medulla caused no significant changes in the mean arterial pressure and heart rate. On the other hand, immunohistochemical study revealed that the receptor for ghrelin, the growth hormone secretagogue receptor, was expressed in the neuronal cells of the nucleus of the solitary tract and the dorsal motor nucleus of the vagus, but not in the cells of the area postrema. These results suggest that ghrelin acts at the nucleus of the solitary tract to suppress sympathetic activity and to decrease arterial pressure in rats. Key Words: blood pressure Ⅲ immunohistochemistry Ⅲ rats G hrelin, an acylated 28-residue peptide originally isolated from rat stomach, is an endogenous ligand for the growth hormone secretagogue (GHS) receptor. 1,2 Although ghrelin is likely to regulate pituitary growth hormone (GH) secretion, along with GH-releasing hormone and somatostatin, 2,3 intracerebroventricular (ICV) administration of ghrelin has been shown to generate a dose-dependent increase in food intake and body weight, 4,5 suggesting that ghrelin participates in the regulation of both food intake and GH secretion.It has been suggested that ghrelin may participate not only in feeding behavior but also in cardiovascular and sympathetic regulation. 6 -10 Ghrelin has a vasodilatory effect in humans, 6 and intravenous injection of human ghrelin has been shown to elicit a decrease in blood pressure without an increase in heart rate (HR) in healthy men. 7 We have recently reported that ICV administration of ghrelin suppresses the renal sympathetic nerve activity (RSNA) and decreases arterial pressure in conscious rabbits, suggesting that intravenous injection of ghrelin acts, at least in part, on the central nervous system to decrease arterial pressure and RSNA. 8 Moreover, ICV administration of ghrelin augments baroreflex control of RSNA and HR. 8 Our previous finding...
