The effects of pretreatment with prostaglandin E2 or the platelet-activating factor antagonist, CV-3988, on endotoxin-induced gastric damage, gastrointestinal plasma protein leakage, and systemic hypotension were examined in the rat. Endotoxic shock was induced by intravenous administration of lipopolysaccharide from Escherichia coli and was characterized by prolonged hypotension, gastrointestinal hyperemia and hemorrhage, and marked leakage of radiolabeled albumin into the interstitium and lumen of the gastrointestinal tract. Prostaglandin E2 (25–100 μg/kg i.v.) dose-dependently inhibited the hypotension and gastric damage induced by endotoxin. At the dose tested, CV-3988 (10 mg/kg i.v.) also significantly reduced endotoxin-induced hypotension and gastric damage. Both prostaglandin E2 (50 μg/kg) and CV-3988 reduced endotoxin-induced plasma protein leakage into the interstitium and lumen of the gastrointestinal tract, although there were differences in terms of the regions most affected by the two compounds. The results of the present study suggest that prostaglandin E2 and CV-3988 may have acted via a similar mechanism, possibly involving inhibition of a mediatory role of platelet-activating factor in endotoxic shock.
Effect of the platelet-activating factor antagonist, TCV-309, and the cyclo-oxygenase inhibitor, ibuprofen, on the haemodynamic changes in canine experimental endotoxic shock