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lar effects of hypocretin-1 in nucleus of the solitary tract. Am J Physiol Heart Circ Physiol 284: H1369-H1377, 2003. First published December 12, 2002 10.1152/ajpheart.00877.2002Experiments 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 urethaneanesthetized 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 Ͼ2.5 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 g/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 HYPOCRETIN (Hcrt) neuropeptides have been recently shown to be almost exclusively expressed within neurons of the lateral and perifornical hypothalamic areas (30,33,35,47,49). These peptides, Hcrt-1, a 33 amino-acid peptide with an NH 2 -terminal pyrogutalmyl residue, and Hcrt-2, a 28 amino acid peptide with a COOH-terminal amide (35), are de-