EFFECT OF A 5-LIPOXYGENASE INHIBITOR, AL-3264, ON PROPRANOLOL-INDUCEDBRONCHOCONSTRICTION IN GUINEA-PIGS

The administration of propranolol can provoke bronchoconstriction in a sthmatic patients. We hypothesized that such bronchoconstriction may r esult from the inflammatory mediators released by an allergic reaction . We investigated the effect of AL-3264, a 5-lipoxygenase inhibitor, o n propranolol-induced bronchoconstriction (PIE) after antigen inhalati on in passively sensitized and artificially ventilated guinea-pigs. Ou r goal was to determine whether products of arachidonate 5-lipoxygenas e are involved in such PIE. Bronchoconstriction occurred when 10 mg/ml of propranolol was inhaled 20 min after antigen challenge. Pretreatme nt with AL-3264 given in intravenous doses of 0.01 and 0.1 mg/kg 15 mi n after the antigen challenge significantly reduced PIE in a dose-depe ndent manner. Pretreatment with 0.1 mg/kg of AL-3264 10 min before ant igen challenge significantly inhibited both the immediate allergic bro nchoconstriction and PIE, although the effect was minimal. Results sug gest that arachidonate 5-lipoxygenase products (such as leukotriene B- 4, C-4, D-4 Or E(4)) are involved in the pathophysiology of PIB but th eir contribution may be small. Further studies using selective antagon ists for each of these leukotrienes are needed to clarify their role.