The relationship between tissue levels of cyclic GMP and tracheal smooth muscle relaxation in the guinea-pig.

The effect of cyclic GMP was investigated using guinea-pig tracheal smooth muscle. 8-Bromo-cyclic GMP showed a dose-dependent relaxation of spontaneous tension of tracheal smooth muscle. Administration of sodium nitroprusside induced dose-dependent relaxation of tracheal smooth muscle as well as an increase in tissue levels of cyclic GMP. Nicorandil, N-(2-hydroxyethyl) nicotinamide nitrate showed dose-dependent relaxation of tracheal smooth muscle and an increase in cyclic GMP levels in the tissue. N-(2-aminoethyl) nicotinamide dihydrochloride, which is a nicorandil derivative and differs minimally in its molecular structure (-NH2 vs -NO2), had neither a relaxant effect on tracheal smooth muscle nor did it increase the level of cyclic GMP in the tissue. The rise cyclic GMP levels preceded the relaxation of tracheal smooth muscle induced by sodium nitroprusside. These results suggest that cyclic GMP is one of the relaxant factors and that nitro-derivatives exhibit their relaxant effect on the smooth muscle mediated by an increase in cyclic GMP level.