ROLE OF LEUKOTRIENES IN POST-ALLERGIC PROPRANOLOL-INDUCED BRONCHOCONSTRICTION IN GUINEA-PIGS

Background Administration of propranolol can provoke bronchoconstricti on only in asthmatic patients. Recently we developed an animal model f or propranolol-induced bronchoconstriction (PIB). Our working hypothes is is that such bronchoconstriction may result from the inflammatory m ediators released by an allergic reaction. Objectives Our goal in this study was to determine which products of arachidonate 5-lipoxygenase pathway are involved in the PIB. Methods Propranolol at a concentratio n of 10 mg/mL was inhaled 20 min after antigen challenge in passively sensitized, anaesthetized and artificially ventilated guinea-pigs. Two different sulfidopeptide leukotriene (s-LT) antagonists, ICI198 615 i n the doses of 0.03 and 0.3 mg/kg and vehicle and KCA757 in the doses of 1 and 5 mg/kg and vehicle, and a LTB4 antagonist ONO4057 in the dos es of 1 and 10 mg/kg and vehicle were injected intravenously 15 min af ter antigen challenge. Effects of an anticholinergic agent atropine su lphate (5 mg/kg) and an alpha-adrenergic blocker phentolamine (0.3 and 3 mg/kg) were examined in the same way. Results Bronchoconstriction o ccurred when 10 mg/mL of propranolol was inhaled 20 min after antigen challenge. Both ICI198 615 and KCA757 administered intravenously 15 mi n after antigen challenge reduced the PIB in a dose-dependent manner w hile ONO4057 did not alter the PIB. Atropine or phentolamine did not c hange the PIB. Conclusions These results suggest that mediator mechani sm, but not cholinergic or alpha-adrenergic nerve, is important in the PIB which developed after the allergic bronchoconstriction in our gui nea-pig model and that s-LTs but not LTB4 have an important role in th e pathophysiology of the PIB.