Oxygen free radicals abolish endothelium-dependent relaxation in diabetic rat aorta

The present experiments were conducted to determine whether endothelium-dependent relaxation is impaired in chronic (10-12 wk), streptozotocin-induced diabetic rat aortas and to determine the specificity and sensitivity of diabetic vasculature to oxygen-derived free radicals. Endothelium-dependent relaxation by acetylcholine and ADP was severely impaired in diabetic rat aorta, whereas endothelium-independent relaxation by nitroglycerin or papaverine was not impaired. Exposure to a free radical-generating system of xanthine plus xanthine oxidase caused a marked and prolonged relaxation in diabetic but not control vessels. Relaxation could not be prevented by the cyclooxygenase inhibitor indomethacin or the lipoxygenase inhibitor nordihydroguaiaretic acid but was attenuated or blocked by catalase. After free radical exposure, aortic rings were washed, reequilibrated, and contracted with a submaximal concentration of norepinephrine. In free radical-exposed vessels, endothelium-dependent relaxation by acetylcholine was reduced by 50% in nondiabetic vessels and abolished in diabetic vessels. Nevertheless, diabetic vessels could still be fully relaxed by nitroglycerin or papaverine. These results suggest selective impairment of endothelium-dependent relaxation in chronic diabetic rat aortas with particular sensitivity to free radical-induced damage.