SR-140333 PREVENTS POTENTIATION BY CITRIC-ACID OF PLASMA EXUDATION INDUCED BY HISTAMINE IN AIRWAYS

We here report a model of potentiation by citric acid of airway microv ascular leakage induced by histamine and its modification by the tachy kinin NK1 and NK2 receptor antagonists, SR 140333 n-3-yl]ethyl}-phenyl -1-azoniabicyclo[2.2.2]octane, chloride) and SR 48968 piperidino)-2-(3 ,4-dichlorophenyl-butyl]benzamide. Guinea-pigs exposed to an aerosol o f citric acid 0.4 M for 1 h developed 24 h later a hyperresponsiveness to histamine-induced microvascular leakage measured by Evans blue dye extravasation. SR 140333, but not SR 48968 (1 mg kg(-1) given each on ce 30 min before citric acid exposure), prevented this potentiation. T hese results provide further evidence of the role of tachykinin and ta chykinin NK1 receptor stimulation on airway hyperresponsiveness and it s neurogenic inflammatory component.