Calcium channel blockers have been shown to modify acute antigen-induced bronchoconstriction in allergic animals and in some human subjects with bronchial asthma; however, the effects of calcium antagonists on late-phase bronchial responses are not known. In this investigation, we studied the effects of calcium antagonist gallopamil on antigen-induced early- and late-phase bronchial responses in sheep allergic to Ascaris suum antigen. In 11 unsedated sheep, specific lung resistance (SRL) was measured before, immediately after, and serially up to 8 h after inhalation challenge with A. suum antigen. On different experiment days, at least 3 wk apart, the sheep were pretreated with gallopamil, administered either as an aerosol (5 mg, n = 10; 10 mg, n = 9) or as an intravenous injection (20 μg/kg, n = 10), and the antigen challenge was repeated. For the control experiments (n = 11), mean ± SE SRL increased immediately after antigen challenge (early response) to 533 ± 72% of baseline and again 6 to 8 h after challenge (late response) to 304 ± 31% of baseline (p < 0.05). Neither intravenously administered nor aerosolized gallopamil had a significant effect on baseline SRL. Both aerosolized and intravenously administered gallopamil blunted the early response and completely blocked the late-phase bronchoconstrictor response (p < 0.05). Mean SRL during early phase increased to 208 ± 39% and 245 ± 39% of baseline with 5 mg and 10 mg of aerosolized gallopamil and to 191 ± 35% of baseline with intravenously administered gallopamil, respectively. During the late phase, mean SRL increased to 109 ± 6%, 139 ± 14%, and 126 ± 13% of baseline with aerosol (5 mg and 10 mg) and intravenously administered gallopamil, respectively; these values were not significantly different from their respective baselines. These data suggest that the calcium antagonist gallopamil attenuates early- and late-phase allergic airway responses and thus may be of potential clinical use.
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine