title: U50,488H-induced pressor effect in the ovine foetus is mediated by sympathetic activation and vasopressin.
abstract: The purpose of this study was to investigate the mechanism behind the increase in blood pressure observed after intravenous administration of U50,488H (trans-3,4-dichloro-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide), a selective Kappa-opioid receptor agonist, to the ovine foetus. Intravenous administration of U50,488H (1.0 mg/kg) to the foetus resulted in an immediate increase in foetal blood pressure which lasted 15 min. Pretreatment with phentolamine (1.0 mg/kg i.v.) completely blocked the immediate (1-4 min) pressor effect of U50,488H, but not the subsequent increase in blood pressure after 5 min. In contrast, pretreatment with the vasopressin antagonist ([beta-mercapto-beta, beta-cyclopentamethylene-propionyl)-O-Me2-Tyr,Arg8]vasopressin, 0.06 mg/kg) did not affect the immediate pressor effect of U50,488H, but completely blocked the latter increase in blood pressure after 4 min. These data suggest that the immediate increase in blood pressure caused by U50,488H was mediated by sympathetic activation which was then further sustained by a release of vasopressin.
authors.affiliation: Department of Pharmacology, Cornell University Medical College, New York, NY 10021, USA.
authors.forename: H H
authors.initials: HH
authors.lastname: Szeto
authors.forename: D
authors.initials: D
authors.lastname: Wu
authors.forename: J S
authors.initials: JS
authors.lastname: Yee
authors.forename: Y
authors.initials: Y
authors.lastname: Soong
authors.forename: S
authors.initials: S
authors.lastname: Fukuda
authors.forename: C T
authors.initials: CT
authors.lastname: Taylor
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D005333:Fetus / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D010646:Phentolamine / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D012756:Sheep; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D014667:Vasopressins / Q000502:physiology*
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D000959:Antihypertensive Agents; D011759:Pyrrolidines; D014667:Vasopressins; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D010646:Phentolamine