Effects of BRL 55 834 on allergen-induced bronchoconstriction and airway inflammation in sensitized guinea pigs

Objective To investigate the effects of potassium channel activator on alle rgen-induced bronchoconstriction and airway inflammation and to discuss whi ch role it plays in asthma therapy. Methods Airway insufflation pressure, examination of inflammatory cells in bronchial alveolar lavage fluid, analysis of airway pathology and airway Ev ans blue dye extravasation measurement were employed to detect airway resis tance and airway inflammatory responses. Results [(3s, 4R)-3,4-dihydro-2,2-dimethyl-4-(2-oxopiperidin-l-yl) -6- pent afluoroethyl-2H-1-benzopyran-3 -ol] (BRL) 55 834 (8 mu g/kg) inhibited not only ovalbumin-induced airway insufflation pressure increase but also infla mmatory cell infiltration (ICI) in sensitized guinea-pigs; moreover, it did not decrease blood pressure; in contrast to BRL 55 834, single dose of BRL 38 227 (200 mu g/kg) and verapamil (0.5 mg/kg) had a little effect on ICI; single dose of aminophylline (25 mg/kg) and dexamethasone (1 mg/kg) could not inhibit ICI, but the former could inhibit airway insufflation increase; drugs, besides aminophylline, could reduce microvascular leakage; single d ose of BRL 38 227, verapamil and dexamethasone had no inhibition of airway insufflation pressure; BRL 38 227 and verapamil decreased blood pressure ma rkedly. Conclusions Selective potassium channel activator BRL 55 834 not only decre ases airway resistance, but also inhibit airway inflammation, and both of t hem are of benefit to asthma therapy.