Effect of a 5-lipoxygenase inhibitor, AL-3264, on propranolol-induced bronchoconstriction in guinea-pigs

The administration of propranolol can provoke bronchoconstriction in asthmatic patients. We hypothesized that such bronchoconstriction may result from the inflammatory mediators released by an allergic reaction. We investigated the effect of AL-3264, a 5-lipoxygenase inhibitor, on propranolol-induced bronchoconstriction (PIB) after antigen inhalation in passively sensitized and artificially ventilated guinea-pigs. Our goal was to determine whether products of arachidonate 5-lipoxygenase are involved in such PIB. Bronchoconstriction occurred when 10 mg/ml of propranolol was inhaled 20 min after antigen challenge. Pretreatment with AL-3264 given in intravenous doses of 0.01 and 0.1 mg/kg 15 min after the antigen challenge significantly reduced PIB in a dose-dependent manner. Pretreatment with 0.1 mg/kg of AL-3264 10 min before antigen challenge significantly inhibited both the immediate allergic bronchoconstriction and PIB, although the effect was minimal. Results suggest that arachidonate 5-lipoxygenase products (such as leukotriene B4, C4, D4 or E4) are involved in the pathophysiology of PIB but their contribution may be small. Further studies using selective antagonists for each of these leukotrienes are needed to clarify their role.