Cardiopulmonary and gastric ulcerogenic actions of endothelin-1 in the guinea pig and rat.
The cardiovascular and bronchoconstrictor actions of endothelin-1 (ET-1) in the anesthetized guinea pig and the cardiovascular effects and gastric ulcerogenic actions in the anesthetized rat were investigated. In the guinea pig, ET-1 (0.05-1 nmol/kg i.v.) induced a dose-related increase in pulmonary inflation pressure, which was substantially inhibited by pretreatment with indomethacin and the thromboxane receptor antagonist BM 13.177. The concurrent vasopressor effects of ET-1 were attenuated but not abolished by these agents. In the rat, ET-1 (0.1-0.4 nmol/kg i.v.) induced a biphasic effect on arterial blood pressure (BP), with a transient fall being followed by a rise, which was unaffected by indomethacin pretreatment, whereas i.v. infusion of ET-1 induced only an increase in BP. Local intra-arterial infusion of ET-1 (0.04-0.1 nmol/kg/min) induced extensive macroscopically determined gastric mucosal damage in the rat, confirmed histologically. Thus, the pharmacological profile of ET-1 encompasses bronchoconstriction, vasopressor and vasodepressor actions, as well as potent gastric ulcerogenic properties.
Whittle
B J
BJ
Department of Pharmacology, Wellcome Research Laboratories, Kent, England.
Payne
A N
AN
Esplugues
J V
JV
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D016232:Endothelins; D005753:Gastric Mucosa / Q000187:drug effects; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration / Q000187:drug effects*; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000503:physiopathology; D013449:Sulfonamides / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D016232:Endothelins; D010455:Peptides; D013449:Sulfonamides; C040624:sulotroban; D007213:Indomethacin