Lawson D L, Mehta J L, Nichols W W
Department of Medicine, University of Florida College of Medicine, Gainesville 32610.
Free Radic Biol Med. 1990;8(4):373-80. doi: 10.1016/0891-5849(90)90103-p.
Previous studies indicate that release of superoxide radicals during coronary reperfusion following occlusion may relate to the loss of endothelium-dependent coronary arterial relaxation. We examined coronary arterial ring relaxation in dogs subjected to temporary circumflex (Cx) coronary artery occlusion and treated with saline or the superoxide radical scavenger superoxide dismutase (SOD). In dogs treated with saline, Cx coronary ring relaxation in response to leukotriene D4 (LTD4) and acetylcholine (ACh) was attenuated (p less than 0.01), but coronary relaxation in response to nitroglycerin was preserved, suggesting loss of endothelium-dependent relaxation following coronary reperfusion. In contrast, Cx coronary relaxation in response to LTD4 and ACh was preserved in the SOD-treated dogs (p less than 0.01 compared to saline-treated dogs). To further examine the role of superoxide radicals in the loss of endothelium-dependent relaxation, normal nonischemic canine coronary artery and rat aortic rings were exposed to a superoxide radical generating system of xanthine and xanthine oxidase in vitro. Xanthine plus xanthine oxidase treatment caused a significant (p less than 0.01) decrease in the relaxant effects of ACh. Pretreatment of rat aortic rings with SOD protected against the loss of ACh-induced relaxation. These observations suggest that release of superoxide radicals during reperfusion is the basis of loss of endothelium-dependent coronary arterial relaxation. Treatment with superoxide radical scavengers prior to coronary reperfusion protects against this loss.
先前的研究表明，冠状动脉闭塞后再灌注期间超氧阴离子自由基的释放可能与内皮依赖性冠状动脉舒张功能丧失有关。我们检测了接受临时左旋支（Cx）冠状动脉闭塞并给予生理盐水或超氧阴离子自由基清除剂超氧化物歧化酶（SOD）治疗的犬冠状动脉环舒张情况。在用生理盐水治疗的犬中，Cx冠状动脉环对白三烯D4（LTD4）和乙酰胆碱（ACh）的舒张反应减弱（p<0.01），但对硝酸甘油的冠状动脉舒张反应得以保留，提示冠状动脉再灌注后内皮依赖性舒张功能丧失。相比之下，在接受SOD治疗的犬中，Cx冠状动脉对LTD4和ACh的舒张反应得以保留（与生理盐水治疗的犬相比，p<0.01）。为了进一步研究超氧阴离子自由基在内皮依赖性舒张功能丧失中的作用，将正常非缺血犬冠状动脉和大鼠主动脉环在体外暴露于黄嘌呤和黄嘌呤氧化酶的超氧阴离子自由基生成系统。黄嘌呤加黄嘌呤氧化酶处理导致ACh舒张作用显著降低（p<0.01）。用SOD预处理大鼠主动脉环可防止ACh诱导的舒张功能丧失。这些观察结果表明，再灌注期间超氧阴离子自由基的释放是内皮依赖性冠状动脉舒张功能丧失的基础。在冠状动脉再灌注前用超氧阴离子自由基清除剂治疗可防止这种丧失。
