Different ability of verapamil to inhibit agonist-induced contraction of lung parenchymal strips from control and sensitized guinea pigs.

There is increasing interest in the therapeutic potential of calcium channel blockers in asthma, but the basic mechanism of this beneficial effect is not fully understood. In the present work we have compared the effect of verapamil on contractions of lung parenchymal strips induced by various agonists (CaCl2, KCl, acetylcholine and histamine) in control (unsensitized) and actively sensitized guinea pigs. Concentration-response curves to CaCl2 were constructed in the presence of a depolarizing (K+ 30 mM) Ca2+-free Tris-physiological salt solution. Verapamil produced a concentration-dependent antagonism of the CaCl2, KCl, acetylcholine and histamine concentration-related responses in control and sensitized preparations. Verapamil inhibited KCl-induced contractions to a greater extent than those induced by acetylcholine and histamine in control and sensitized specimens. The ability of verapamil to inhibit CaCl2-, KCl-, acetylcholine- and histamine-induced contractions was substantially reduced in sensitized tissues compared to control. These results may be interpreted as supporting the hypothesis of an increased Ca2+ influx linked to airway hyperreactivity and point to the contribution of other sites of action, besides airways smooth muscle, to the beneficial effect of calcium channel blockers in asthma.