title: Effect of endothelin on the function of the isolated perfused working rat heart.
abstract: 1. The effect of endothelin on the performance of the isolated perfused working rat heart has been examined. 2. A low concentration of endothelin (60 pmol/l) produced a gradual but sustained increase in cardiac output; coronary vascular resistance was unaffected. 3. A high concentration of endothelin (600 pmol/l) produced a rapid increase in cardiac output, followed by a marked fall in cardiac output as progressive, severe coronary vasoconstriction developed. 4. The coronary vasoconstriction induced by endothelin (600 pmol/l) was partially blocked by nicardipine (0.5 mumol/l). 5. In the presence of either nicardipine (0.5 mumol/l) or verapamil (0.2 mumol/l), the increment in cardiac output induced by endothelin (600 pmol/l) was greater than that induced by the addition of the same concentration of endothelin to hearts which had not been exposed to calcium-entry blockers. 6. The effect of endothelin on myocardial contractility has a different time course, concentration dependence and response to calcium-entry blockade than the effect on the coronary vasculature. This suggests that different mechanisms are involved in the generation of the myocardial and vascular responses to endothelin.
authors.affiliation: Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Headington, Oxford, U.K.
authors.forename: J D
authors.initials: JD
authors.lastname: Firth
authors.forename: A F
authors.initials: AF
authors.lastname: Roberts
authors.forename: A E
authors.initials: AE
authors.lastname: Raine
mesh_terms: D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D016232:Endothelins; D004730:Endothelium, Vascular / Q000187:drug effects*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009529:Nicardipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013318:Stroke Volume / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
chemical_list: D016232:Endothelins; D010455:Peptides; D014700:Verapamil; D009529:Nicardipine