THE EFFECT OF INHALED VERAPAMIL ON RESTING BRONCHIAL TONE AND AIRWAY CONTRACTIONS INDUCED BY HISTAMINE AND ACETYLCHOLINE IN NORMAL AND ASTHMATIC SUBJECTS

Publisher Website
Google Scholar
Abstract
In man, the influence of Ca entry blockers (CEB) on nonspecific bronchial sensitivity and resting bronchial tone is controversial. In 10 asthmatic and 8 normal subjects specific airway conductance (Gaw/VL) and flow volume loops were recorded before, 30, 60, and 90 min after the inhalation of saline, 10 (V10) of verapamil. The dose of inhaled histamine and acetylcholine producing Gaw/VL of -40% (PD40H and PD40ACH, respectively) with and without pretreatment with saline, V10, and, in 15 subjects, V20 was also determined. Plasma verapamil concentrations were measured immediately after the end of nebulization of V10 and V20, and 30 and 60 min later. In normal subjects, V10 and V20 produced a maximal %.DELTA.Gaw/VL of 22.30 (.+-. 19.50) and 33.00 (.+-. 15.82), respectively (P < 0.05). In asthmatics, V10 and V20 produced comparable %.DELTA.Gaw/VL of 22.00 (.+-. 22.50) and 38.60) (.+-. 38.60), respectively. This bronchodilating effect involved predominantly the large airways, persisted for 60-90 min, was reproducible, affected only some subjects (11 of 18), and was independent of the resting Gaw/VL, degree of bronchial sensitivity to H and ACH, and the time course of plasma verapamil concentration. The latter reached a maximum of 24.3 .+-. 7.1 ng/ml after V20. In both normal and asthmatic subjects, saline or V10 did not significantly alter PD40H and PD40ACH. In normal subjects, pretreatment with V20 increased PD40H 5.3 times (P < 0.05). Except in 2 asthmatics, in whom V20 decreased PD40 and PD40ACH, it increased significantly PD40ACH (dose ratio: 3.15, P < 0.05) but not PD40H. The effect of V20 on PD40ACH was unrelated to resting Gaw/VL or pretreatment PD50. High doses of inhaled verapamil, despite low plasma levels, can evidently dilate the bronchi of asthmatic and normal subjects. In normal subjects, V20 exerts a mild antihistamine and anticholinergic activity. In asthmatic subjects, V20 has a variable effect.