Increased airways responsiveness to histamine induced by platelet activating factor in the guinea-pig: possible role of lipoxygenase metabolites.
In anaesthetized guinea-pigs pretreated with propranolol (1 mg/kg, i.v.), platelet activating factor (Paf, 0.02 micrograms/kg, i.v.) caused an acute increase in airways response to histamine (0.5-3.0 micrograms/kg, i.v.) measured as intratracheal pressure. Treatment with the cyclooxygenase inhibitors, aspirin (10 mg/kg, i.v.) or indomethacin (5 mg/kg, i.v.), enhanced the magnitude and duration of this effect but a combined lipoxygenase/cyclooxygenase inhibitor, BW 755C (20 mg/kg, i.v.), prevented the increase in responsiveness. In aspirin treated animals, a putative lipoxygenase inhibitor NDGA (10 mg/kg, i.v.). or atropine methyl nitrate (1 mg/kg, i.v.) or bilateral vagotomy reduced the magnitude of Paf-induced increased histamine responses but did not prevent the effect. Bronchoconstriction induced by Paf was variably influenced by the drug treatments. These data suggest that Paf causes an acute increase in airways responsiveness to histamine in the guinea-pig through a mechanism that may, in part, be dependant on the release of lipoxygenase metabolites.