Effects of inhibitors of arachidonic acid metabolism on Paf-induced gastric mucosal necrosis and haemoconcentration.

The effects of several inhibitors of arachidonic acid metabolism on gastric necrosis, hypotension, haemoconcentration, leukopenia and plasma exudation induced by platelet-activating factor (Paf) were studied in the rat. A 10 min intravenous infusion of Paf (100 ng kg-1 min-1) caused extensive gastric damage and a marked fall in systemic blood pressure which had not recovered to basal levels 30 min after the infusion had been terminated. Paf also caused significant haemoconcentration, plasma exudation and transient leukopenia. Pretreatment with dexamethasone (0.2 or 2 mg kg-1 s.c.) or prednisolone (20 mg kg-1 s.c.) two hours before Paf significantly reduced the gastric damage and accelerated the recovery of blood pressure after the Paf infusion. Likewise, BW755C (50 mg kg-1 p.o.) significantly reduced the gastric damage. Acute pretreatment with dexamethasone (2 mg kg-1 i.v.) 15 min before Paf, or with indomethacin (5 mg kg-1 s.c.), acetylsalicylic acid (10 mg kg-1 i.v.) or 1-benzylimidazole (50 mg kg-1 s.c.) did not significantly affect the gastric damage induced by Paf. The Paf-induced haemoconcentration and plasma exudation were significantly reduced by pretreatment with prednisolone (20 mg kg-1 s.c.) or BW755C (50 mg kg-1 p.o.), while Paf-induced leukopenia was unaffected by either drug. These studies indicate that cyclo-oxygenase products of arachidonic acid are unlikely to contribute significantly to the gastric damage or the prolonged hypotension induced by Paf. The ability of corticosteroids and BW755C to reduce the gastric damage, haemoconcentration and plasma exudation suggests that lipoxygenase products of arachidonic acid may contribute to these actions of Paf.