Effect of nipradilol, a new beta-blocker, on leukotriene D4-induced contraction in guinea pig tracheal smooth muscle.

Abstract

The relaxant effect on smooth muscle of nitro compounds is suggested to be linked with the increase in the tissue level of cyclic GMP by activating guanylate cyclase. In this study, we investigated the effects of nipradilol, a new beta-blocker, which has NO2 residue in the molecular structure, and isosorbide dinitrate (ISDN) on guinea pig tracheal smooth muscle in comparison with the effect of propranolol. Nipradilol and ISDN showed dose-dependent relaxant effects on leukotriene (LT) D4-induced contraction of tracheal smooth muscle, though propranolol had no effect. 8-Bromo-cyclic GMP also showed a relaxant effect dose dependently. Nipradilol and ISDN elevated cyclic GMP levels in tracheal tissue dose dependently; however, propranolol caused no change in cyclic GMP levels. From these results, it is suggested that nipradilol relaxes LTD4-induced contraction of tracheal smooth muscle by increasing the tissue level of cyclic GMP.