Differential effects of hydrogen peroxide on indices of endothelial cell function.

Abstract

The responses of pig aortic endothelial cells to sublethal doses of potentially toxic stimuli were investigated by monitoring K+ efflux, prostaglandin [PG] production and the release of cytoplasmic purines. Xanthine plus xanthine oxidase reversibly stimulated these 3 parameters of endothelial cell function at doses that were not cytotoxic asmeasured by Ch release, adenine uptake and vital dye exclusion. The effects of xanthine plus xanthine oxidase were inhibited by catalase but not by superoxide dismutase, suggesting that H2O2 was responsible. Reagent H2O2 also reversibly stimulated K+ efflux, prostaglandin production and the release of purines. The threshold concentration of H2O2 for these effects was .apprx. 10 .mu.M, which was at least 30-fold lower than that which caused cytotoxicity. In addition to the direct effect of H2O2 in stimulating prostaglandin production (PGI2 and PGE2), prior exposure of endothelial cells to lower doses of H2O2 (< 0.1 .mu.M) at high O2 tension inhibited the subsequent stimulation of prostaglandin production by ATP, A23187 [calcimycin] and H2O2 itself. H2O2 apparently has substantial effects on endothelial physiology at doses up to 3,000-fold lower than those which induce cytotoxicity.