Role of oxygen-derived free radicals in the impairment of endothelium-dependent relaxations caused by elevated glucose

Endothelium-dependent relaxations (EDR) are impaired in isolated normal arteries exposed to elevated glucose in vitro and in arteries of diabetic animals. The role of oxygen-derived free radicals in the impairment of EDR by glucose was studied with antioxidant enzymes, deferoxamine, probucol, and by determining and sensitivity to free radicals generated by xanthine oxidase. Rings of abdominal aorta suspended for measurement of isometric tension were incubated for 6 hours in control or elevated glucose. Impairment of EDR to acetylcholine caused by exposure to elevated glucose was prevented by catalase, superoxide dismutase, or deferoxamine indicating that generation of oxygen-derived free radicals play a role in the abnormality. Xanthine oxidase-induced free radicals caused contractions which were significantly larger in rings incubated in elevated glucose. In aorta from rabbits treated with probucol for six weeks, exposure to elevated glucose had no significant effect on acetylcholine relaxation. These findings indicate that oxygen-derived free radicals participate in the endothelial cell dysfunction caused by exposure to elevated glucose. In vivo treatment with probucol protects against the in vitro effects of exposure to elevated glucose suggesting that lipid peroxidation may play a role in the impairment of EDR.