EXPRESSION OF PROSTAGLANDIN-H SYNTHASE-2 IN ENDOTOXIC-SHOCK INDUCED IN RATS

We investigated the expression of prostaglandin H synthase-2 in rats s ubjected to endotoxic shock. The prostaglandin H synthase activities w ere assessed by measuring the plasma prostaglandins (PGE(2) and 6-keto -PGF(1x)) after arachidonic acid administration (3 mg/kg, i.v.). The p lasma prostaglandin concentrations increased immediately after adminis tration of arachidonic acid, reached a peak at 30-60 seconds. and then rapidly decreased. Lipopolysaccharide (1 mg/kg, i.v.) also increased the plasma prostaglandin concentrations, reached a peak I hour after a dministration, and then gradually decreased to normal levels. The prod uction of plasma prostaglandin, induced by administration of arachidon ic acid, was markedly enhanced in the lipopolysaccharide-treated rats. A low dose of acetylsalicylic acid (3 mg/kg, i.v.) blocked the prosta glandin production in the nontreated rats but not in the lipopolysacch aride-treated rats. In the latter group of rats, a high dose of acetyl salicylic acid (30 mg/kg, i.v.), given 10 to 30 minutes before adminis tration of arachidonic acid. completely blocked the prostaglandin prod uction, but recovery of this production was seen with acetylsalicylic acid (30 mg/kg) treatment at 1 to 2 hours before administration of ara chidonic acid. These data suggest that pretreatment with lipopolysacch aride enhances the prostaglandin production by forming newly synthesiz ed prostaglandin H synthase. Immunoblots of the levels of enzyme prote in from rat aorta endothelial cells were analyzed. The enzyme protein cross-reacting with antibody against prostaglandin H synthase-2 was in creased by lipopolysaccharide treatment in endothelial cells, and was constitutively expressed in the stomach. kidney and liver. but not in the lung and the intestine. The induction of prostaglandin H synthase- 2 by lipopolysaccharide treatment was observed only in endothelial cel ls. The enhancement of the prostaglandin production in lipopolysacchar ide-treated rats was blocked by pretreatment with dexamethasone, prior to administration of lipopolysaccharide, this suppression is apparent ly the result of a decrease of the prostaglandin H synthase-2 protein in endothelial cells, as determined by Western blotting. The enhanced production of prostaglandin, induced by lipopolysaccharide, seems to b e due to the in vivo expression of prostaglandin H synthase-2.