Effects of hydrogen peroxide on vascular arachidonic acid metabolism

Hydrogen peroxide (H2O2) released by granulocytes during phagocytosis has previously been demonstrated to affect the function of other cellular elements including red cells and platelets. We have evaluated the effect of H2O2 on vascular arachidonic acid (AA) metabolism. Exposure of human vascular segments to H2O2 (25 to 200 microM) results in a concentration dependent inhibition in the ability of these vessels to produce PGI2 either from endogenous stores of AA, or from exogenously provided substrate. The inhibition of PGI2 production was present at 5 minutes post addition of H2O2, with maximal inhibitory effect occurring by 15 minutes. Production of 6 Keto PGF1 alpha from exogenously provided 14C AA was similarly inhibited in isolated microsomes from these vessels, as was the production of the other vascular cyclo-oxygenase metabolites PGE2 and PGF2 alpha. These results demonstrate that the major effect of H2O2 on vascular AA metabolism appears to occur at the cyclo-oxygenase level. Vascular inhibition of PGI2 formation caused by the local release of H2O2 from phagocytizing cellular elements may play a role in the pathophysiology of the inflammatory process.