title: Mechanisms of centrally administered ET-1-induced increases in systemic arterial pressure and AVP secretion.
abstract: Endothelins (ET) within the central nervous system (CNS) alter systemic cardiovascular responses and arginine vasopressin (AVP) secretion. These experiments were designed to ascertain whether the rise in systemic arterial pressure after central administration of ET-1 is mediated by enhancing sympathetic outflow and/or circulating AVP. In Long-Evans (LE/LE) rats, intracerebroventricular injection of 1-10 pmol ET-1 dose dependently increased mean arterial pressure (MAP). Peak response occurred 7-12 min after ET-1 and was inhibited by ETA receptor antagonism. Systemic vasopressin (V1) receptor blockade did not inhibit the pressor response, and rats with central diabetes insipidus (DI/DI) displayed an identical rise in MAP. Ganglionic blockade prevented ET-1-induced hemodynamic effects. Peak plasma AVP levels occurred 60 min after ET-1, as the pressor response began to wane. In sinoaortic-denervated LE/LE rats, ET-1 elicited a 10-fold increase in AVP secretion that coincided with the hemodynamic changes and was blocked by BQ-123. Thus ET-1 via ETA receptors within the CNS induced a concentration-dependent increase in systemic arterial pressure mediated by enhanced sympathetic outflow but not by circulating AVP. Reflex baroreceptor activation attenuated AVP release.
authors.affiliation: Department of Medicine, Wayne State University School of Medicine, Detroit 48201, USA.
authors.forename: N F
authors.initials: NF
authors.lastname: Rossi
authors.forename: D S
authors.initials: DS
authors.lastname: O'Leary
authors.forename: H
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000502:physiology*; D002714:Chlorisondamine / Q000494:pharmacology; D003714:Denervation; D003919:Diabetes Insipidus / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D005730:Ganglionic Blockers / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012850:Sinus of Valsalva / Q000294:innervation; D013997:Time Factors
chemical_list: D065128:Endothelin Receptor Antagonists; D005730:Ganglionic Blockers; D001127:Arginine Vasopressin; D002714:Chlorisondamine