The inhibitory effects of nicorandil, nitroglycerin and isosorbide dinitrate on the contractions induced by 10(-6) M norepinephrine or by 65.4 mM K+ were compared in the vascular smooth muscle of rabbit aorta. These compounds relatively selectively inhibited the contraction induced by norepinephrine. Norepinephrine induced a sustained contraction in the aorta depolarized with high K+ and treated with 10(-6) M verapamil, and this contraction was also inhibited by these compounds. The increase in Ca2+ influx induced by norepinephrine, but not by high K+, was inhibited by the three compounds. The norepinephrine-induced transient contraction, which is due to release of stored Ca2+, was inhibited by these compounds. The inhibitory effects of nicorandil and nitroglycerin on this contraction were attenuated by high-K+ depolarization. Methylene blue (10(-5) M) antagonized and M&B 22948 (10(-5) M) potentiated the inhibitory effects of these compounds. These results suggest that nicorandil, nitroglycerin and isosorbide dinitrate have a similar mechanism of action. These compounds inhibit the norepinephrine-induced sustained contraction possibly by inhibiting the Ca2+ influx through receptor-linked Ca2+ channels, and inhibit the transient contraction by membrane hyperpolarization and also by direct inhibition of Ca2+ release although other mechanism of action may also be involved.