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

Abstract

To investigate the effects of potassium channel activator on allergen-induced bronchoconstriction and airway inflammation and to discuss which role it plays in asthma therapy. Airway insufflation pressure, examination of inflammatory cells in bronchial alveolar lavage fluid, analysis of airway pathology and airway Evans blue dye extravasation measurement were employed to detect airway resistance and airway inflammatory responses. [(3s, 4R)-3, 4-dihydro-2, 2-dimethyl-4-(2-oxopiperidin-l-yl)-6-pentafluoroethyl-2H-1-benzopyran-3-ol] (BRL) 55 834 (8 micrograms/kg) inhibited not only ovalbumin-induced airway insufflation pressure increase but also inflammatory 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 micrograms/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 dose of BRL 38 227, verapamil and dexamethasone had no inhibition of airway insufflation pressure; BRL 38 227 and verapamil decreased blood pressure markedly. Selective potassium channel activator BRL 55 834 not only decreases airway resistance, but also inhibit airway inflammation, and both of them are of benefit to asthma therapy.