U50,488H-induced pressor effect in the ovine foetus is mediated by sympathetic activation and vasopressin.
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.
Szeto
H H
HH
Department of Pharmacology, Cornell University Medical College, New York, NY 10021, USA.
Wu
D
D
Yee
J S
JS
Soong
Y
Y
Fukuda
S
S
Taylor
C T
CT
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*
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