Time course and mechanism of endothelial dysfunction in isolated ischemic- and hypoxic-perfused rat hearts.
Time course and mechanism of endothelial dysfunction in isolated ischemic- and hypoxic-perfused rat hearts.
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离体缺血和缺氧灌注大鼠心脏内皮功能障碍的时间过程和机制。
DOI：
10.1152/ajpheart.1990.259.6.h1660
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Lefer,AM
中科院分区：
文献类型：
--
作者：
Tsao,PS;Lefer,AM
离体灌流大鼠心脏进行全脑缺血30分钟，然后再灌注2.5，5，10，或20分钟，然后进行测试的反应性内皮依赖性血管扩张剂乙酰胆碱（ACh）和内皮非依赖性血管扩张剂硝酸甘油（NTG）。再灌注后2.5分钟ACh舒张功能受损（为初始对照的32 ± 3%，P <0.01），此后每次均持续抑制。在任何时间，血管扩张剂对NTG的反应均未显著降低。内皮功能障碍的重组人超氧化物歧化酶（hSOD，5毫克/心脏），但不是由羟基自由基清除剂N-（2-巯基丙酰基）-甘氨酸（8毫克/心脏）的预防。比较的效果和类似的时间过程中观察到缺氧心脏再氧期长达20分钟。化学发光的灌注流出物作为一个指标的自由基生产在所有postreperfusion时间在缺血性心脏测量。仅局部缺血引起化学发光的小幅增加。然而，再灌注，产生显着更高的化学发光增加，在0.25分钟，这是由hSOD阻断的活性的大爆发。这些研究结果表明，内皮功能障碍导致内皮源性舒张因子释放减少发生在再灌注或复氧后的早期，可能是由于超氧自由基的作用。
Isolated perfused rat hearts were subjected to global ischemia for 30 min followed by reperfusion for 2.5, 5, 10, or 20 min and then were tested for responsiveness to the endothelium-dependent vasodilator acetylcholine (ACh) and the endothelium-independent vasodilator nitroglycerin (NTG). ACh relaxation was impaired 2.5 min after reperfusion (32 +/- 3% of initial control, P less than 0.01) and remained comparably depressed at every time thereafter. No significant decrease in vasodilator response to NTG occurred at any time. Endothelial dysfunction was prevented by recombinant human superoxide dismutase (hSOD, 5 mg/heart) but not by the hydroxyl radical scavenger N-(2-mercaptopropionyl)-glycine (8 mg/heart). Comparable effects and a similar time course were observed in hypoxic hearts reoxygenated for periods up to 20 min. Chemiluminescence of perfusion effluent employed as an index of free radical production was measured at all postreperfusion times in ischemic hearts. Ischemia alone produced small increases in chemiluminescence. Reperfusion, however, produced significantly higher increases in chemiluminescence, with a large burst of activity at 0.25 min, which was blocked by hSOD. These findings suggest that endothelial dysfunction resulting in decreased release of endothelium-derived relaxing factor occurs very early after reperfusion or reoxygenation and may be due to the action of superoxide free radicals.