Pieper G M, Gross G J
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.
Am J Physiol. 1988 Oct;255(4 Pt 2):H825-33. doi: 10.1152/ajpheart.1988.255.4.H825.
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.
进行本实验以确定慢性（10 - 12周）链脲佐菌素诱导的糖尿病大鼠主动脉中内皮依赖性舒张功能是否受损，并确定糖尿病血管对氧衍生自由基的特异性和敏感性。糖尿病大鼠主动脉中乙酰胆碱和ADP介导的内皮依赖性舒张功能严重受损，而硝酸甘油或罂粟碱介导的非内皮依赖性舒张功能未受损。暴露于黄嘌呤加黄嘌呤氧化酶的自由基生成系统会导致糖尿病血管而非对照血管出现显著且持久的舒张。环氧合酶抑制剂吲哚美辛或脂氧合酶抑制剂去甲二氢愈创木酸无法阻止这种舒张，但过氧化氢酶可使其减弱或阻断。自由基暴露后，主动脉环经冲洗、重新平衡，并用次最大浓度的去甲肾上腺素收缩。在暴露于自由基的血管中，非糖尿病血管中乙酰胆碱介导的内皮依赖性舒张功能降低50%，而糖尿病血管中则完全消失。然而，糖尿病血管仍可被硝酸甘油或罂粟碱完全舒张。这些结果表明，慢性糖尿病大鼠主动脉中内皮依赖性舒张功能存在选择性损伤，且对自由基诱导的损伤具有特殊敏感性。
