Vasorelaxing action of nicorandil, in comparison with nitroglycerin and Ca antagonists.

Vasorelaxing effects of nicorandil, a new antianginal drug, were examined in isolated rat thoracic aorta and compared with those of nitroglycerin and Ca antagonists (verapamil and diltiazem). Nicorandil at concentrations over 10(-7) M produced a potent relaxation in norepinephrine-contracted aortic strips, and the EC50 was 2.2 X 10(-6) M. The relaxing pattern varied between the different concentrations of nicorandil. At 10(-5) M, the response was transient; after the peak relaxation, the tension gradually returned to the precontracted level. Rhythmic contraction occurred during the recovery. At a higher concentration (10(-4) M), the relaxation lasted for more than 30 min. In the aortic strips which had been treated with Ca antagonists beforehand, nicorandil at all concentrations tested produced a long lasting relaxation, and the rhythmic contraction did not appear during exposure to nicorandil. Pharmacological analyzing experiments revealed that nicorandil at concentrations lower than 10(-5) M inhibits intracellular Ca release and the receptor-operated Ca channel, but that at higher concentrations the voltage-dependent Ca channel is also inhibited. Nitroglycerin produced a transient relaxation by mechanisms similar to those proposed at low concentration of nicorandil. Ca antagonists selectively inhibited the voltage-dependent Ca channel. From these results, it is suggested that nicorandil has both the pharmacological profiles of nitroglycerin and Ca antagonists.