Effect of nicorandil on the excitation-contraction coupling in smooth muscle cells of the rabbit ear artery.

The effects of nicorandil on excitation-contraction coupling in the ear artery of the rabbit have been investigated. Perivascular nerve stimulation induces excitatory junction potentials (e.j.p.'s) and action potentials, which can be inhibited by nicorandil. The inhibition of the nerve-evoked responses by nicorandil cannot be due to an effect of nicorandil on neurotransmitter metabolism because of its failure to inhibit the release of 3H-noradrenaline from the nerve terminals. The decreased excitability of the smooth muscle cells can be partially explained by the increase of K permeability, as measured by 87Rb efflux, and by the concomitant hyperpolarization of the cell membrane. Because the inhibitory action of nicorandil on the contractile responses also occurs in K-depolarized tissues in which nicorandil no longer affects the membrane potential, additional mechanisms of action have to be sought. A study of 45Ca exchange under these conditions does not suggest that this relaxing effect is mediated by changes in cytoplasmic Ca.