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 myocar dial ischemic and reperfusion injury in the isolated rat heart. Bosent an (10(-5) M) attenuated coronary constriction induced by ET-1 and dil atation induced by the ET(B) 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 ventricul ar developed pressure, dP/dt(max), and coronary flow at the end of rep erfusion, compared to vehicle-treated controls. During reperfusion, le ft ventricular end-diastolic pressure was significantly lower in the b osentan group than in the vehicle group. Acetylcholine-induced, endoth elium-dependent vasodilatation was significantly attenuated at the end of reperfusion in controls but not in bosentan-treated hearts. We con clude that bosentan reduces myocardial and endothelial injury after is chemia/reperfusion in the isolated rat heart, indicating a pathophysio logic role of endogenous ET.