Abstract
Nicorandil is a K(ATP) channel opener, nitric oxide donor and antioxidant, and is used as a drug for the treatment of angina pectoris. This durg induces cardioprotection and vasodilatation after ischemia reperfusion. It was previously reported that nicorandil may exert antiarrhythmic actions by abolishing both spontaneous and triggered activity [early after‐depolarization (EADs), delayed after‐depolarization (DADs)] (Lathrop et al., Br J Pharmacol, 1990). The triggered activity induced by DADs is one of the mechanisms of ventricular arrhythmias associated with intracellular Ca2+ overload.In this study we examined the effect of nicorandil on Na+/Ca2+ exchange current (INCX) in isolated guinea pig ventricular myocytes using the whole‐cell patch clamp technique.Nicorandil enhanced INCX in a concentration‐dependent manner. The EC50 values of nicorandil were 15.0 μM and 8.7 μM for the outward and inward components of INCX, respectively. Eight‐Br‐cGMP, a membrane permeable analog of cGMP also enhanced the INCX in a concentration‐dependent manner. ODQ, a guanylate cyclase inhibitor (10 µM) almost completely abolished the effects of both nicorandil and Eight ‐Br‐cGMP on INCX. DADs induced by electrical stimulation with ouabain disappeared in the presence of 100 µM nicorandil. We conclude that nicorandil enhances the function of Na+/Ca2+ exchanger (NCX) via guanylate cyclase, and this may partially contribute to the cardioprotection of nicorandil by acceleratiing Ca2+ exit via NCX.
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