Lipoxygenase metabolites mediate increased airways responsiveness to histamine after acute platelet activating factor exposure in the guinea-pig.

Platelet activating factor (Paf, 0.02 micrograms/kg, i.v. bolus) caused an acute increase in airways responsiveness to histamine in anaesthetized guinea-pigs prepared for recording airways resistance (RL) and dynamic compliance (Cdyn). Aspirin pretreatment (10 mg/kg, i.v.) attenuated the return of airways responsiveness to prechallenge levels. Pretreatment with the combined cyclooxygenase/lipoxygenase inhibitors BW 755C (20 mg/kg, i.v.) and ETYA (20 mg/kg, i.v.), or with the putative cysteinyl-containing leukotriene antagonist FPL 55712 (0.25 mg/kg/min, i.v.), or a Paf antagonist SRI 63441 (2.5 mg/kg, i.v.), prevented Paf-induced increased airways responsiveness. Inhibitors of leukotriene synthesis, BW 755C and ETYA, or action, FPL 55712, had variable effects on Paf-induced bronchoconstriction. These data suggest that lipoxygenase metabolites, possibly leukotrienes, may mediate an acute increase in airways responsiveness to histamine after Paf exposure.