HYDROXYL RADICALS MEDIATE INJURY TO ENDOTHELIUM-DEPENDENT RELAXATION IN DIABETIC RAT

The purpose of this study was to determine the radical species which m ediates the toxic effects of exogenous oxygen-derived free radicals on endothelial function of chronic diabetic rat aorta. Endothelium-depen dent relaxation to acetylcholine was impaired in diabetic vessels. Exp osure to the exogenous free radical generating system of xanthine plus xanthine oxidase selectively impaired endothelium-dependent relaxatio n to acetylcholine in control and diabetic aorta with relaxations esse ntially abolished in diabetic aorta. The loss of relaxation to acetylc holine in diabetic aorta was prevented or attenuated by pretreatment w ith catalase, dimethylthiourea or desferrioxamine, but not by mannitol or superoxide dismutase. These results suggest that hydroxyl radicals play an important role in the endothelial injury produced by oxygen-d erived free radicals in chronic diabetic rat aorta. Furthermore, the s ite of the injury is likely due to intracellular generation of hydroxy l radicals.