Effects of nicorandil and its interaction with isoproterenol on force of contraction and cyclic nucleotide levels of canine atrial muscle: comparison with carbachol.

Experiments were carried out on isolated canine right atria to investigate the effects of N-(2-hydroxyethyl)nicotinamide nitrate (nicorandil, SG-75) and its interaction with beta-adrenoceptor stimulation on the cyclic nucleotide levels accompanying inotropic changes. The results were compared with those during muscarinic receptor stimulation. The effects of nicorandil were similar to those of carbachol insofar as its negative inotropic effect was accompanied by a significant elevation of cyclic GMP levels in the absence of beta-adrenoceptor stimulation. However, the effects of nicorandil differed strikingly from those of carbachol in that the negative inotropic action of nicorandil was readily counteracted by isoproterenol, while that of carbachol was not. This difference may be ascribed to differences in cyclic AMP metabolism caused by these agents: carbachol but not nicorandil decreased the isoproterenol-induced elevation of cyclic AMP levels. The negative inotropic effects of muscarinic receptor stimulation on canine atria are associated with two different sorts of changes in cyclic nucleotide metabolism, i.e., cyclic GMP elevation and cyclic AMP reduction; nicorandil mimics the former but not the latter process.