title: Endothelin dilates bovine pulmonary circulation and reverses hypoxic pulmonary vasoconstriction.
abstract: To assess the effects of endothelin 1 (ET) on the pulmonary and systemic vascular beds simultaneously, we examined the hemodynamic responses to ET in awake calves implanted with a Jarvik total artificial heart (TAH), a device that maintains constant cardiac output (CO). During basal conditions, successive incremental intravenous (i.v.) injections of 1, 3, and 10 micrograms ET caused a dose-dependent decrease in pulmonary arterial pressure (PAP), (from 24 +/- 3 to 15 +/- 1 mm Hg, p less than 0.05) while having no effect on systemic arterial (SAP), left atrial (LAP), and right atrial (RAP) pressures. Administration of 30 micrograms ET i.v. also decreased PAP, had no effect on LAP and RAP, but increased SAP from 100 +/- 6 to 118 +/- 4 mm Hg (p less than 0.05). The decrease in PAP was rapid, occurring within seconds and lasting 10 min, whereas the increase in SAP occurred after 2-5 min and was prolonged for greater than or equal to 20 min. As compared with injection in the right atrium, administration of 30 micrograms ET into the left atrium reduced PAP to a similar extent, but induced a greater increase in SAP (+32.5 +/- 4 vs +17.5 +/- 2 mm Hg, p less than 0.05). ET also dose-dependently reversed the acute pulmonary vasoconstriction induced by inhalation of an hypoxic gas mixture. In all cases, pulmonary vasodilation occurred without evidence of short-term tolerance. The results demonstrate that ET is a potent in vivo pulmonary vasodilator. In calves, the predominant hemodynamic response to ET is pulmonary vasodilation, with systemic vasoconstriction apparent only at higher concentrations of the peptide.
authors.affiliation: Département de Physiologie, Hôpital Henri Mondor, Créteil, France.
authors.forename: P H
authors.initials: PH
authors.lastname: Deleuze
authors.forename: S
authors.initials: S
authors.lastname: Adnot
authors.forename: N
authors.initials: N
authors.lastname: Shiiya
authors.forename: F
authors.initials: F
authors.lastname: Roudot Thoraval
authors.forename: S
authors.initials: S
authors.lastname: Eddahibi
authors.forename: P
authors.initials: P
authors.lastname: Braquet
authors.forename: P E
authors.initials: PE
authors.lastname: Chabrier
authors.forename: D Y
authors.initials: DY
authors.lastname: Loisance
mesh_terms: D000208:Acute Disease; D000818:Animals; D002302:Cardiac Output / Q000502:physiology; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D000860:Hypoxia / Q000188:drug therapy* / Q000503:physiopathology; D011652:Pulmonary Circulation / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D016232:Endothelins; D014665:Vasodilator Agents