title: Mechanisms of cardiovascular actions of urocortins in the hypothalamic arcuate nucleus of the rat.
abstract: The presence of urocortins (UCNs) and corticotropin-releasing factor (CRF) receptors has been reported in the hypothalamic arcuate nucleus (ARCN). We have previously reported that UCNs are involved in central cardiovascular regulation. Based on this information, we hypothesized that the ARCN may be one of the sites where UCNs exert their central cardiovascular actions. Experiments were done in artificially ventilated, adult male Wistar rats anesthetized with urethane. Unilateral microinjections (30 nl) of UCN1 (0.12-2 mM) elicited decreases in mean arterial pressure (MAP) and heart rate (HR). Maximum cardiovascular responses were elicited by a 1 mM concentration of UCN1. Microinjections of UCN2 and UCN3 (1 mM each) into the ARCN elicited similar decreases in MAP and HR. UCN1 was used as a prototype for the other experiments described below. HR responses elicited by UCN1 were significantly attenuated by bilateral vagotomy. Prior microinjections of NBI-27914 (CRF-1 receptor antagonist) and astressin (CRF-1 receptor and CRF-2 receptor antagonist) (1 mM each) into the ARCN significantly attenuated the cardiovascular responses elicited by UCN1 microinjections at the same site. Microinjections of UCN1 into the ARCN decreased efferent renal sympathetic nerve activity. It was concluded that microinjections of UCN1, UCN2, and UCN3 into the ARCN elicited decreases in MAP and HR. Decreases in MAP, HR, and renal sympathetic nerve activity elicited by UCN1 microinjections into the ARCN were mediated via CRF receptors. Bradycardic responses to UCN1 were mediated via the activation of vagus nerves, and decreases in MAP may be mediated via decreases in sympathetic nerve activity.
authors.affiliation: Department of Neurological Surgery, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA.
authors.forename: Vineet C
authors.initials: VC
authors.lastname: Chitravanshi
authors.forename: Kazumi
authors.initials: K
authors.lastname: Kawabe
authors.forename: Hreday N
authors.initials: HN
authors.lastname: Sapru
mesh_terms: D000768:Anesthesia, General; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D062186:Arterial Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects* / Q000294:innervation*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006727:Hormone Antagonists / Q000008:administration & dosage; D007668:Kidney / Q000187:drug effects / Q000294:innervation; D008297:Male; D008845:Microinjections; D009292:Narcotic Antagonists / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000187:drug effects / Q000378:metabolism; D058468:Receptors, Ionotropic Glutamate / Q000187:drug effects / Q000378:metabolism; D012121:Respiration, Artificial; D013564:Sympathetic Nervous System / Q000187:drug effects*; D054832:Urocortins / Q000008:administration & dosage*; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects* / Q000601:surgery; D000099052:CRF Receptor, Type 1
chemical_list: C101531:CRF receptor type 2; D018691:Excitatory Amino Acid Antagonists; D006727:Hormone Antagonists; D009292:Narcotic Antagonists; D018019:Receptors, Corticotropin-Releasing Hormone; D058468:Receptors, Ionotropic Glutamate; D054832:Urocortins; D000099052:CRF Receptor, Type 1
keywords: N-methyl-d-aspartic acid; blood pressure; heart rate; microinjection; sympathetic nerve activity