Effects of endothelin-1 on the rat isolated heart.

This study shows that bolus injections of endothelin-1 (ET-1) (1-30 pmol) produce transient vasodilator and prolonged coronary vasoconstrictor actions. The initial effect on cardiac contractility was a positive inotropic action, but with repeated doses a negative inotropic action developed. Verapamil (0.1 microM) antagonized the vasoconstrictor action of Bay K 8644 but did not affect ET-1-induced vasoconstriction. In contrast, removal of extracellular calcium did block the vasoconstrictor action of ET-1. This suggests that vasoconstriction is due to activation of receptor-rather than potential-operated calcium channels. The ET-1-induced vasoconstriction was not due to the release of platelet-activating factor (PAF) or thromboxane A2 since it was not inhibited by WEB 2086 (0.5 microM), fluribiprofen (2 microM), or BW755C (7 microM). In addition, thromboxane B2 could not be detected in the effluent from the heart. The vasoconstrictor action of ET-1 was potentiated by passage of air through the coronary vascular bed, suggesting that an intact endothelium normally opposes this vasoconstrictor effect.