The possible involvement of endothelin-1 (ET-1) and angiotensin II in the coronary vasoconstriction induced by nitric oxide synthase (NOS) inhibition was investigated in isolated Langendorff-perfused rat hearts. Fifteen minutes of perfusion with the NOS inhibitor N G-nitro-L-arginine (L-NNA, 0.1 mM) reduced coronary flow by 31%. Pre-treatment with the non-selective ETA/ETB receptor antagonist bosentan (1 and 10 μM) attenuated this reduction in coronary flow to 16% (P < 0.05) and 8% (P < 0.01), respectively. The selective ETA receptor antagonist BQ-123 (1 μM) induced a similar inhibitory action, whereas the selective ETB receptor antagonist BQ-788 and the angiotensin II type 1 receptor antagonist candesartan did not affect the vasoconstrictor response to L-NNA. In addition, bosentan administered after 15 min of L-NNA perfusion reversed the L-NNA-induced reduction in coronary flow in a dose-dependent manner. The high concentration of bosentan (10 μM) increased the basal coronary flow by 17%, while the lower concentration of bosentan, BQ-123, BQ-788 and candesartan did not affect basal coronary flow. Bosentan (10 μM) increased the level of ET-like immunoreactivity (-LI) in the coronary effluent twofold. L-NNA did not affect ET-LI level. These results indicate that ET-1 contributes to the coronary vasoconstrictor effect of L-NNA in the isolated rat heart, and that this action of ET-1 is mediated through ETA receptor activation. Angiotensin II does not seem to contribute to L-NNA-induced vasoconstriction under the present condition.