The nonpeptide endothelin receptor antagonist bosentan enhances myocardial recovery and endothelial function during reperfusion of the ischemic rat heart.
We investigated the effects of bosentan, a nonpeptide endothelin (ET) receptor antagonist, on ET-induced changes in coronary flow and myocardial ischemic and reperfusion injury in the isolated rat heart. Bosentan (10(-5) M ) attenuated coronary constriction induced by ET-1 and dilatation induced by the ETB agonist IRL 1620. In hearts subjected to 30 min of global ischemia followed by 30 min of reperfusion, bosentan (10(-5) M) significantly improved the recoveries of the left ventricular developed pressure, dP/dtmax, and coronary flow at the end of reperfusion, compared to vehicle-treated controls. During reperfusion, left ventricular end-diastolic pressure was significantly lower in the bosentan group than in the vehicle group. Acetylcholine-induced, endothelium-dependent vasodilatation was significantly attenuated at the end of reperfusion in controls but not in bosentan-treated hearts. We conclude that bosentan reduces myocardial and endothelial injury after ischemia/reperfusion in the isolated rat heart, indicating a pathophysiologic role of endogenous ET.
Wang
Q D
QD
Department of Cardiology, Karolinska Hospital, Stockholm, Sweden.
Li
X S
XS
Pernow
J
J
D000818:Animals; D000077300:Bosentan; D003326:Coronary Circulation / Q000187:drug effects; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D015425:Myocardial Reperfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000627:therapeutic use*
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D013449:Sulfonamides; D000077300:Bosentan