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

Abstract

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.

Platelet-Activating Factor–Induced Ischemic Bowel Necrosis: The Effect of Platelet-Activating Factor Acetylhydrolase

“…The effects of the various treatments on the plasma PAF-AH at the end of 2 h are summarized in Table 2. The administration of PAF caused a profound hemoconcentration due to increased vascular permeability (18).…”

Gastric Bleeding and Increased Gastric Vascular Permeability Induced by Platelet Activating Factor(PAF):Effect of Drugs that Affect Arachidonate Metabolism.

“…On the other hand, 1-benzylimidazole, an in hibitor of thromboxane (TX) synthesis, has no effect on the formation of PAF-induced gastric damage (8). PGE2 and its 16,16-dimethyl ana logue potentiate the formation of PAF-in duced gastric damage (10).…”

“…The effects of drugs modifying the arachidonate metabolism on the PAF-induced gastric mucosal damage have been reported, but the data have not been consistent with each other, probably because of differences in dose or route of drug administration. For inst ance, glucocorticoid steroids such as dexa methasone or prednisolone prevent formation of PAF-induced gastric damage (8) or have no effect (9). Moreover, NSAIDs such as in domethacin or aspirin aggravate PAF-induced gastric damage (2) or produce no change (8).…”

“…Glucocorti coid steroids such as dexamethasone or pred nisolone prevent formation of PAF-induced gastric damage (8) or have no effect (9). Non steroidal antiinflammatory drugs (NSAIDs) such as indomethacin or aspirin aggravate PAF-induced gastric damage (2) or produce no change (8). Prostaglandin E2 (PGE2) po tentiates formation of PAF-induced gastric damage (10).…”

“…At present, how ever, findings on the effects of drugs affecting arachidonate metabolism on PAF-induced gas tric damage are very controversial. Glucocorti coid steroids such as dexamethasone or pred nisolone prevent formation of PAF-induced gastric damage (8) or have no effect (9). Non steroidal antiinflammatory drugs (NSAIDs) such as indomethacin or aspirin aggravate PAF-induced gastric damage (2) or produce no change (8).…”