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.