Leukotriene A4-induced bronchoconstriction in the guinea pig in vivo

Administration of leukotriene A4 (0.03-0.3 microgram 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.