Effects of hydrogen peroxide on vascular arachidonic acid metabolism

Hydrogen peroxide (H 2O 2) 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 H 2O 2 on vascular arachidonic acid (AA) metabolism. Exposure of human vascular segments to H 2O 2 (25 to 200 μM) results in a concentration dependent inhibition in the ability of these vessels to produce PGI 2 either from endogenous stores of AA, or from exogenously provided substrate. The inhibition of PGI 2 production was present at 5 minutes post addition of H 2O 2 , with maximal inhibitory effect occurring by 15 minus. Production of 6 Keto PFG 1α 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 PGE 2 and PGF 2α. These results demonstrate that the major effect of H 2O 2 on vascular AA metabolism appears to occur at the cyclo-oxygenase level. Vascular inhibition of PGI2 formation caused by the local release of H 2O 2 from phagocytizing cellular elements may play a role in the pathophysiology of the inflammatory process.