Pharmacological characterization of effects of nifedipine on isolated guinea-pig and rat tracheal smooth muscle.

Nifedipine, a relatively new Ca2+-channel blocking agent, has recently been shown to be effective in the treatment of exercise-induced asthma; however, the pharmacological mechanism by which it blocks bronchospasm is little understood. We have investigated and characterized its effects on the reactivity of isolated guinea-pig and rat tracheal smooth muscle. Although it (10(-8)--10(-7)M) blocked the contraction of the rat tracheal muscle to KCl and CaCl2, nifedipine (10(-7)--10(-6)M) did not significantly inhibit histamine, methacholine or serotonin-induced muscle contractions in guinea-pigs and the methacholine contraction in rats. Nifedipine produced a potent relaxation on contracted tracheal muscle. The concentration required to produce 50% relaxation on 10(-5)M histamine-precontracted guinea-pig tracheal muscle was 8.31 +/- 3.12 X 10(-9)M, and the extent of the nifedipine-induced relaxation could be modified by the baseline and active contracted tension. Nifedipine was more potent in producing the relaxation in guinea-pig tracheal muscle than isoproterenol, theophylline or verapamil. However, the time required for 50% relaxation by 3 X 10(-5)M isoproterenol was significantly less than the time for the nifedipine (3 X 10(-5)M) or verapamil (10(-4)M) effect. In addition, the Hill number of the nifedipine-induced relaxation was different from the value of the isoproterenol or verapamil effect. Our results indicate that nifedipine exerts a potent dilatory effect directly on airway muscle, and suggest that such effect could be one of its pharmacological actions on relieving bronchospasm.