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 μM) 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 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 PGE₂ and PGF_2α. 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.