INHIBITION OF BRONCHOCONSTRICTION IN THE GUINEA-PIG BY A CALCIUM-CHANNEL BLOCKER, NIFEDIPINE

Abstract

The inhibitory effects of nifedipine, a Ca channel blocker were investigated on airway smooth muscle constriction in the guinea pig. In vitro, nifedipine (0.003-3.0 .mu.M) caused significant dose-dependent reversal of intrinsically existing tone in both tracheal spirals and parenchymal strips. Nifedipine also inhibited the constriction of tracheal spirals and parenchymal strips induced by 2 different agonists, histamine and carbachol. At a concentration of 3.0 .mu.M nifedipine increased by 48-fold the concentration of carbachol required to produce a 50% of maximal contraction of parenchymal strips, and by 5-fold the concentration of histamine. Increasing extracellular Ca concentration in the tissue baths significantly diminished the inhibitory action of nifedipine. In vivo, nifedipine (30 .mu.g/kg body wt given i.v.) did not alter pulmonary resistance or dynamic compliance. It did attenuate histamine-induced bronchoconstriction in 3 of 5 animals studied. In response to the maximal dose of histamine infused, mean pulmonary resistance rose 40 .+-. 16% (SEM [standard error of the mean]) after nifedipine vs. 182 .+-. 65% in the control animals (P < 0.025) and mean dynamic compliance decreased 35 .+-. 8% after nifedipine vs. 58 .+-. 6% in the control animals (P < 0.01). This Ca2+ channel blocker apparently inhibits mediator-induced constriction of central and peripheral airway contractile tissues, a finding of potential clinical applicability for human patients.