Leukotriene A4-induced bronchoconstriction in the guinea pig in vivo

Administration of leukotriene A₄ (0.03 - 0.3 μg kg^?1 i.v.) to anesthetized spontaneously breathing guinea pigs produced pronounced changes in pulmonary resistance, dynamic compliance and blood pressure. The pulmonary responses were unaffected either by pretreatment with indomethacin or following desensitization to leukotriene B₄ but were significantly attenuated by the leukotriene D₄ receptor antagonist, FPL-55712. Following administration of leukotriene A₄ increased levels of leukotriene C₄-immunoreactive material were determined in the plasma and neutrophil accumulation was observed in the lung. It was concluded that leukotriene A₄ induced bronchoconstriction in the guinea pig either by acting directly on the leukotriene D₄ receptor site or more probably through efficient metabolism in the lung to peptido-lipid leukotrienes which in turn exerted direct bronchoconstrictor actions.