The effect of inhaled verapamil on resting bronchial tone and airway contractions induced by histamine and acetylcholine in normal and asthmatic subjects.
In man, the influence of calcium entry blockers (CEB) on nonspecific bronchial sensitivity and resting bronchial tone is controversial. In 10 asthmatic and 8 normal subjects we recorded specific airway conductance (Gaw/VL) and flow volume loops before, 30, 60, and 90 min after the inhalation of saline, 10 (V10) and 20 mg (V20) 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. We measured plasma verapamil concentrations 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 less than 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 to 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 and PD40ACH 3.22 times (p less than 0.05). Except in 2 asthmatics, in whom V20 decreased PD40 and PD40ACH, it increased significantly PD40ACH (dose ratio: 3.15, p less than 0.05) but not PD40H.(ABSTRACT TRUNCATED AT 250 WORDS)
D000109:Acetylcholine / Q000494:pharmacology*; D000328:Adult; D000403:Airway Resistance / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects*; D001985:Bronchial Provocation Tests; D001986:Bronchial Spasm / Q000139:chemically induced / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012123:Pulmonary Ventilation / Q000187:drug effects; D012016:Reference Values; D012119:Respiration; D012146:Rest; D014700:Verapamil / Q000008:administration & dosage* / Q000627:therapeutic use
D006632:Histamine; D014700:Verapamil; D000109:Acetylcholine