Effects of antagonists for endothelin ET(A) and ET(B) receptors on coronary endothelial and myocardial function after ischemia-reperfusion in anesthetized goats.
To compare the effects of antagonists for endothelin ET(A) and ET(B) receptors on the action of ischemia-reperfusion on endothelial and myocardial function, 30 min of partial or total occlusion followed by 60 min of reperfusion of the left circumflex coronary artery was induced in anesthetized goats treated with intracoronary administration of saline (vehicle), BQ-123 (endothelin ET(A) receptors antagonist) or BQ-788 (endothelin ET(B) receptors antagonist). During reperfusion after partial occlusion, coronary vascular conductance and left ventricle dP/dt were decreased after saline or BQ-788, and they normalized after BQ-123. In these three groups of animals, the coronary effects of acetylcholine (3-100 ng) and sodium nitroprusside (1-10 microg) during reperfusion were as under control. During reperfusion after total occlusion, coronary vascular conductance and left ventricle dP/dt were decreased after saline, and they normalized after BQ-123 or BQ-788. In these three groups of animals, the coronary effects of acetylcholine but not those of sodium nitroprusside during reperfusion were decreased after saline, and they reversed after BQ-123 or BQ-788. Therefore, selective antagonists of endothelin ET(B) and ET(A) receptors may produce similar protection of coronary vasculature and myocardium against reperfusion after severe ischemia. Selective antagonists of endothelin ET(B) receptors, contrarily to those of endothelin ET(A) receptors, may be ineffective to protect coronary vasculature and myocardium against reperfusion after mild ischemia.
Climent
Belén
B
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, Arzobispo Morcillo, 2, 28029 Madrid, Spain.
Fernández
Nuria
N
García-Villalón
Angel Luis
AL
Monge
Luis
L
Sánchez
Ana
A
Diéguez
Godofredo
G
D000109:Acetylcholine / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006041:Goats; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics; D023421:Models, Animal; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D044022:Receptor, Endothelin A / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D014665:Vasodilator Agents; D009599:Nitroprusside; C086539:BQ 788; D000109:Acetylcholine; C072247:cyclo(Trp-Asp-Pro-Val-Leu)