Cardiovascular effects of hypocretin-1 in nucleus of the solitary tract

Department of Physiology and Pharmacology, Faculty of Medicine and Dentistry, Health Sciences Center, University of Western Ontario, London, Ontario, Canada N6A 5C1 Experiments were done in male Wistar rats to investigate the effects of microinjection of hypocretin-1 (Hcrt-1) into the nucleus of the solitary tract (NTS) on mean arterial pressure (MAP), heart rate (HR), and the baroreflex. In the first series, the distribution of Hcrt-1-like immunoreactivity (Ir) was mapped within the region of NTS. Hcrt-1 Ir was found throughout the NTS region, predominantly within the caudal dorsolateral (Slt), medial (Sm), and interstitial subnuclei of the NTS. In the second series, in -chloralose or urethane-anesthetized rats, microinjection of Hcrt-1 (0.5-5 pmol) into the caudal NTS elicited a dose-dependent decrease in MAP and HR. A mapping of the caudal NTS region showed that the largest depressor and bradycardia responses elicited by Hcrt-1 were from sites in the Slt and Sm. In addition, doses >2.5 pmol at a small number of sites localized to the caudal commissural nucleus of NTS elicited pressor and tachycardia responses. Intravenous administration of the muscarinic receptor blocker atropine methyl bromide abolished the bradycardia response and attenuated the depressor response, whereas subsequent administration of the nicotinic receptor blocker hexamethonium bromide abolished the remaining MAP response. Finally, microinjection of Hcrt-1 into the NTS significantly potentiated the reflex bradycardia to activation of arterial baroreceptors as a result of increasing MAP by systemic injections of phenylephrine (2-4 µg/kg). These results suggest that Hcrt-1 in the NTS activates neuronal circuits that increases vagal activity to the heart, inhibits sympathetic activity to the heart and vasculature, and alters the excitability of NTS neuronal circuits that reflexly control the circulation. orexin-A; blood pressure; baroreceptor reflex; brain stem; ingestive behavior