Effect of Nifedipine on Dose-Response Curves to Acetylcholine and Histamine Measured during Quiet Breathing

Abstract

We have investigated the effect of nifedipine on acetylcholine-induced bronchoconstriction in 8 asthmatics and on histamine-induced bronchoconstriction in another 8 asthmatics on a single-blind basis. Expiratory spirograms were done at the beginning of the examination in all subjects, and repeated after 10 mg of oral nifedipine or a placebo. The change of respiratory resistance during the inhalation of acetylcholine or histamine was recorded continuously by an Astograph®. Using this device, we were able to obtain the direct-writing dose-response curve of respiratory resistance measured during quiet breathing. Resting airway tone appeared to be generally unaffected by nifedipine, as there was no significant change in baseline spirograms. Nifedipine increased significantly the threshold of bronchial responsiveness, i.e., the cumulative dose of acetylcholine (D_min) at which the respiratory resistance started to increase, compared with placebo (p < 0.02). However, S_d, the slope of the increasing rate of respiratory resistance in the dose-response curve, was not attenuated by nifedipine. In histamine inhalation tests, neither D_min nor S_d were modified by nifedipine. The discrepancy observed between the effects of nifedipine on acetylcholine- and histamine-induced bronchoconstriction may imply that, in asthmatics, nifedipine exerts its effect mainly by stabilizing mast cells rather than by directly inhibiting bronchial smooth muscle contractility. This hypothesis is based on the fact that mast cells have acetylcholine receptors on their surfaces but no histamine H₁-receptors