Superoxide anions and hyperoxia inactivate endothelium-derived relaxing factor. G. M. Rubanyi and P. M. Vanhoutte. Am. J. Physiol. 250 (Heart Circ. Physiol. 19): H822–H827, 1986. Experiments were conducted to determine the effects of oxygen-derived free radicals on the production and biological activity of endothelium-derived relaxing factor (EDRF) or factors released by acetylcholine. Rings of canine coronary arteries without endothelium (bioassay rings) were superfused with solution passing through a canine femoral artery with endothelium. Superoxide dismutase caused maximal relaxation of the bioassay ring when infused upstream, but not downstream, of the femoral artery; this effect was inhibited by catalase. Infusion of acetylcholine relaxed the bioassay rings because it released a labile relaxing factor (or factors) from the endothelium. When infused below the femoral artery, superoxide dismutase and, to a lesser extent, catalase augmented the relaxations to acetylcholine. Superoxide dismutase, but not catalase, doubled the half-life of the endothelium-derived relaxing factor(s). This protective effect of the enzyme was augmented fivefold by lowering the oxygen content of the perfusate from 95 to 10%. These data demonstrate that: 1) superoxide anions inactivate the relaxing factor(s) released by acetylcholine from endothelial cells and 2) hyperoxia favors the inactivation of endothelium-derived relaxing factor(s). The study shows that superoxide anions inactivate EDRF, which is released by acetylcholine from endothelial cells. Hyperoxia accelerates this inactivation. Superoxide dismutase, a specific scavenger of superoxide anions, prolongs the half-life of EDRF, especially under low oxygen conditions. The results suggest that superoxide anions are responsible for the inactivation of EDRF, and that hyperoxia enhances this process. The protective effect of superoxide dismutase is augmented by reducing oxygen levels, indicating that the inactivation of EDRF is influenced by both the concentration of superoxide anions and the rate of their elimination. The study also highlights the role of oxygen tension in the inactivation of EDRF, suggesting that the short half-life of EDRF observed in previous studies may be due to the artificial environment imposed.Superoxide anions and hyperoxia inactivate endothelium-derived relaxing factor. G. M. Rubanyi and P. M. Vanhoutte. Am. J. Physiol. 250 (Heart Circ. Physiol. 19): H822–H827, 1986. Experiments were conducted to determine the effects of oxygen-derived free radicals on the production and biological activity of endothelium-derived relaxing factor (EDRF) or factors released by acetylcholine. Rings of canine coronary arteries without endothelium (bioassay rings) were superfused with solution passing through a canine femoral artery with endothelium. Superoxide dismutase caused maximal relaxation of the bioassay ring when infused upstream, but not downstream, of the femoral artery; this effect was inhibited by catalase. Infusion of acetylcholine relaxed the bioassay rings because it released a labile relaxing factor (or factors) from the endothelium. When infused below the femoral artery, superoxide dismutase and, to a lesser extent, catalase augmented the relaxations to acetylcholine. Superoxide dismutase, but not catalase, doubled the half-life of the endothelium-derived relaxing factor(s). This protective effect of the enzyme was augmented fivefold by lowering the oxygen content of the perfusate from 95 to 10%. These data demonstrate that: 1) superoxide anions inactivate the relaxing factor(s) released by acetylcholine from endothelial cells and 2) hyperoxia favors the inactivation of endothelium-derived relaxing factor(s). The study shows that superoxide anions inactivate EDRF, which is released by acetylcholine from endothelial cells. Hyperoxia accelerates this inactivation. Superoxide dismutase, a specific scavenger of superoxide anions, prolongs the half-life of EDRF, especially under low oxygen conditions. The results suggest that superoxide anions are responsible for the inactivation of EDRF, and that hyperoxia enhances this process. The protective effect of superoxide dismutase is augmented by reducing oxygen levels, indicating that the inactivation of EDRF is influenced by both the concentration of superoxide anions and the rate of their elimination. The study also highlights the role of oxygen tension in the inactivation of EDRF, suggesting that the short half-life of EDRF observed in previous studies may be due to the artificial environment imposed.