Aim To investigate the effect of selective endothelin A receptor (ETA)antagonist BMS-182874 on myocardial ischemia-reperfusion (I-R) injury in isolated rat hearts. Methods The isolated hearts were perfused in a Langendorff mode and acute myocardial ischemic model was induced by 30 min of global ischemia and 30 min of reperfusion. The effects of ETA receptor antagonist BMS-182874 (10 μmol/L, 50 μmol/L) on heart function during reperfusion, the release of cardiac creatine kinase (CK) in the coronary effluent and the content of myocardial tumor necrosis factorα (TNF-α) were analyzed. Results 30-minute global ischemia caused a dramatic decrease in myocardial function, as shown by decreasing LVP, ±dp/dt max ,, CF (p<0.01) and increasing CK release (23.9±2.2 vs 217.5±14.1, p<0.01) and myocardial TNF-α content (645±45 vs 1 926±141, p<0.01). However, treatment with 10 μmol/L and 50 μmol/L BMS-182874 significantly attenuated the ischemia-induced myocardial injury, increased LVP, ±dp/dt max , and reduced the release of CK (185±14, 143±11, compared with ischemia/reperfusion group, p<0.05, p<0.01 respectively) and the TNF-αcontent in myocardial tissues (p<0.01), but had no effect on HR and CF (1222±67, 1108±57, compared with ischemia/reperfusion group, p<0.01). Conclusions These findings suggest the cardioprotective effects afforded by ETA receptor antagonist BMS-182874 may be related to inhibition of myocardial TNF-αproduction.