PHARMACOLOGICAL CHARACTERIZATION OF EFFECTS OF NIFEDIPINE ON ISOLATED GUINEA-PIG AND RAT TRACHEAL SMOOTH-MUSCLE

  • 1 January 1983
    • journal article
    • research article
    • Vol. 263  (2) , 228-244
Abstract
Nifedipine, a new Ca2+-channel blocking agent, is effective in the treatment of exercise-induced asthma, but the pharmacological mechanism by which it blocks bronchospasm is little understood. Its effects on the reactivity of isolated guinea pig and rat tracheal smooth muscle were studied. 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 produced 50% relaxation on 10-5 M histamine-precontracted guinea pig tracheal muscle was 8.31 .+-. 3.12 .times. 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. The time required for 50% relaxation by 3 .times. 10-5 M isoproterenol was significantly less than the time for the nifedipine (3 .times. 10-5 M) or verapamil (10-4 M) effect. The Hill number of the nifedipine-induced relaxation was different from the value of the isoproterenol or verapamil effect. Apparently nifedipine exerts a potent dilatory effect directly on airway muscle. This effect could be one of its pharmacological actions on relieving bronchospasm.