Hypoxia/reoxygenation alters endothelial prostacyclin synthesis—Protection by superoxide dismutase☆

Abstract An in vitro model was designed to study the role of ischemia/reperfusion and oxygen free radicals on vascular prostacyclin (PGI 2 ) synthesis and protection provided by superoxide dismutase (SOD). Cultured bovine aortic endothelial cells (BAEC) were subjected to various times of hypoxia (30 min to 5 h) followed by 30 min reoxygenation. An increase or a decrease in PGI 2 synthesis capacity was then observed according to the duration of hypoxia. Inhibition of PGI 2 synthesis after 5 h hypoxia/30 min reoxygenation was accompanied by a rise in lipoperoxidation products and a slight cytotoxicity. Superoxide anion could be implicated in these cellular alterations as SOD efficiently prevented these effects. Incubation of normoxic of H/R-treated BAEC with SOD led to an increase in cellular SOD activity as compared to controls. This increase, inhibited by incubation at 4°C but not by addition of cycloheximide, strongly suggested endocytosis of SOD. This study emphasizes the role of endothelium as a source and target of free radicals and provides a new insight into the mechanism of protection by SOD in ischemia-related vascular pathology.