ANTIGEN-INDUCED AIRWAY RESPONSES ARE INHIBITED BY A POTASSIUM CHANNELOPENER

We have investigated the effect of a potassium channel opener, BRL 382 27, on antigen-induced bronchoconstriction and airway microvascular le akage in sensitized guinea pigs by simultaneously measuring pulmonary resistance (RL) and extravasation of Evans blue dye. Guinea pigs were sensitized 3 wk before experimentation with ovalbumin (OA) and aluminu m hydroxide. The trachea was cannulated, and lungs were mechanically v entilated. All animals were pretreated 30 min before experimentation w ith atropine (1 mg/kg intravenously) and propranolol 1 mg/kg to block muscarinic and beta-adrenergic responses, respectively. BRL 38227 (200 mu g/kg) was administered intravenously 1 min before intravenous dye injection (30 mg/kg); OA (3 mg/ml) was inhaled using an ultrasonic neb ulizer (for 30 s) 1 min after dye injection. BRL 38227 significantly i nhibited OA-induced bronchoconstrictor response (p < 0.01) and plasma leakage in trachea (p < 0.05) and main bronchi (p < 0.05). BRL 38227 a lso had an inhibitory effect on exogenous histamine- and leukotriene-i nduced bronchoconstriction and microvascular leakage. However, BRL 382 27 did not affect OA-induced histamine release from minced lung tissue s in sensitized guinea pigs. We conclude that the allergic bronchocons trictor response and airway plasma leakage are inhibited by a potassiu m channel opener, possibly as a result of its effect on the airway smo oth muscle and the postcapillary venule level.