The effect of Paf antagonists on bronchial hyperresponsiveness induced by Paf, propranolol or indomethacin

1. Intravenous administration of platelet activating factor, Paf (600 ng kg-1 h-1) to ventilated anaesthetised guinea-pigs induced bronchial hyperresponsiveness to i.v. acetylcholine. 2. Pretreatment of ventilated, anaesthetised guinea-pigs with the beta-adrenoceptor antagonist, propranolol, or the non-steroidal anti-inflammatory drug, indomethacin, induced bronchial hyperresponsiveness to i.v. histamine. 3. Paf-induced bronchial hyperresponsiveness was significantly attenuated by pretreatment with three different Paf antagonists, CV-3988, BN 52021 and WEB 2086. 4. Pretreatment of guinea-pigs with CV-3988, BN 52021 or WEB 2086 at doses inhibiting Paf-induced bronchial hyperresponsiveness, had no significant effect on propranolol or indomethacin-induced bronchial hyperresponsiveness. 5. It is suggested that bronchial hyperresponsiveness induced by propranolol or indomethacin is not secondary to Paf release in the guinea-pig.