ABSTRACT
The effect of endothelin (ET-1) on the function of the isolated perfused working guinea pig has been examined. ET- 1 wasshowed to exert a transient positive inotropic effect on the isolated heart, followed by a marked inhibition of cardiac function. Low dose of ET- 1(30,90 pmol?L-1) produced reversible inhibition. The effect of high dose of ET- 1 was irreversible, accompanied with increasing LDH significantly, indomethacin markedly augmented the vasoconstrictor and cardiac ischemia effects of ET-1. Our results suggest that the apparent inhibition of cardiac function on the isolatedperfused guinea pig heart after administration of ET-1 may be due to the effect of the myocardial ischaemia caused by progressive development of coronary vasoconstriction. In our experimental model, PGI2 has partially antagonizing effect on the vasoconstrictor action of ET-1.