IMPAIRED ENDOTHELIUM-DEPENDENT RELAXATION AFTER CORONARY REPERFUSION INJURY - EVIDENCE FOR G-PROTEIN DYSFUNCTION
IMPAIRED ENDOTHELIUM-DEPENDENT RELAXATION AFTER CORONARY REPERFUSION INJURY - EVIDENCE FOR G-PROTEIN DYSFUNCTION
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DOI：
10.1016/0003-4975(94)90121-x
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发表时间：
1994-06-01
影响因子：
4.6
通讯作者：
SCHAFF, HV
中科院分区：
文献类型：
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作者：
EVORA, PRB;PEARSON, PJ;SCHAFF, HV
本研究旨在探讨G蛋白功能障碍是否可能导致内皮源性舒张因子（EDRF）的受体依赖性释放异常。将狗暴露于全心肌缺血（45分钟，通过主动脉阻断诱导），随后在心肺转流时再灌注（60分钟），然后在器官室实验中在体外研究冠状动脉。再灌注后，内皮依赖性舒张受体依赖性激动剂腺苷二磷酸和乙酰胆碱显着受损，以及氟化钠，其作用于百日咳毒素敏感的G蛋白。相反，内皮依赖性舒张受体非依赖性激动剂A23187和磷脂酶C是正常的。此外，对聚-L-精氨酸（分子量，139，200）的内皮依赖性舒张似乎通过非一氧化氮途径诱导犬冠状动脉的内皮依赖性舒张，不受缺血和再灌注的影响。这些实验表明，全心肌缺血和再灌注选择性损害受体介导的EDRF（一氧化氮）的释放，但内皮细胞产生EDRF或产生内皮依赖性舒张非一氧化氮依赖性激动剂的能力保持不变。我们推测冠状动脉再灌注损伤导致内皮细胞G蛋白功能障碍。
This study was done to determine whether abnormal receptor-dependent release of endothelium-derived relaxing factor (EDRF) might be caused by G-protein dysfunction. Dogs were exposed to global myocardial ischemia (45 minutes, induced by aortic cross-clamping) followed by reperfusion (60 minutes) while on cardiopulmonary bypass, and coronary arteries were then studied in vitro in organ chamber experiments. After reperfusion, endothelium-dependent relaxation to the receptor-dependent agonists adenosine diphosphate and acetylcholine was significantly impaired as well as to sodium fluoride, which acts on a pertussis toxin-sensitive G-protein. In contrast, endothelium-dependent relaxations to the receptor-independent agonists A23187 and phospholipase C were normal. Furthermore, endothelium-dependent relaxation to poly-L-arginine (molecular weight, 139,200), which appears to induce endothelium-dependent relaxation of the canine coronary artery by a nonnitric oxide pathway, was unaffected by ischemia and reperfusion. These experiments suggest that global myocardial ischemia and reperfusion selectively impair receptor-mediated release of EDRF (nitric oxide) but that the ability of the endothelial cell to produce EDRF or generate endothelium-dependent relaxation to nonnitric oxide-dependent agonists remains intact. We hypothesize that coronary reperfusion injury leads to G-protein dysfunction in the endothelium.