The injurious effect of
platelet activating factor (PAF) on gastric mucosa was studied by measuring
bleeding in the
acid perfused stomach of anesthetized rats. The effect of PAF on gastric mucosal vascular permeability (GMVP) was assessed by
dye-leakage in the saline perfused stomach of anesthetized rats.
Intravenous infusion of PAF (100 ng/kg/min for 20 min) apparently caused gastric
bleeding under the gastric
luminal perfusion with 150 mM HCl
solution,, with the peak response at 50-70 min; biopsy indicated the presence of mucosal lesions. GMVP was markedly increased with the peak response at 20-40 min. Pretreatment with
CV-3988 (1 or 10 mg/kg, i.v.), a PAF antagonist, dose-dependently blocked the PAF-induced gastric
bleeding and increase in GMVP. Pretreatment with
hydrocortisone acetate (20 or 40 mg/kg, s.c.) reduced PAF-induced gastric
bleeding and increase in GMVP, in contrast to the aggravation by
caffeic acid (1 or 5 mg/kg, s.c.).
Indomethacin (1 or 5 mg/kg, s.c.) prevented PAF-induced gastric
bleeding, and it depressed the increase in GMVP in the case of the lower dose.
Prostaglandin E2 (50 or 500 micrograms/kg, s.c.) significantly reduced PAF-induced gastric
bleeding, but had little effect on PAF-induced increase in GMVP.
1-Benzylimidazole (10 or 50 mg/kg, s.c.) also inhibited PAF-induced gastric
bleeding and depressed the increase in GMVP at the higher dose. These results suggest that increased GMVP plays a significant role in producing the gastric damage by PAF. Changes in the mucosal level of
cyclooxygenase products, especially
thromboxanes, by drugs modifying the arachidonate metabolism would be closely associated with their prevention or aggravation of gastric damage induced by PAF.