Modification of allergic bronchoconstriction by a calcium antagonist: mode of action

Because both degranulation of mast cells and contraction of airway smooth muscle are dependent upon the influx of calcium, a calcium blocking agent might modify allergic bronchoconstriction by at least these two mechanisms. We treated sheep allergic to Ascaris suum antigen with the calcium antagonist Verapamil prior to airway challenge with an aerosol of Ascaris suum antigen and also investigated the response without pretreatment. Aerosolized Ascaris suum antigen increased mean pulmonary resistance (RL) to 530% of baseline (n = 6). Pretreatment with intravenously administered Verapamil (150 micrograms/kg) increased mean RL to 225% of baseline but bronchoconstriction produced by subsequent antigen challenge was completely prevented. Verapamil did not modify bronchoconstriction produced by aerosols of histamine and carbachol, agents that act upon airway smooth muscle. Further, it did not reverse the increase in RL induced by an intravenous infusion of carbachol. These results suggest that verapamil, at the dosage used, did not prevent allergic bronchoconstriction by a direct action on smooth muscle and therefore was effective by inhibiting the release of mast cell mediators.