Attenuated coronary relaxation after reperfusion: effects of superoxide dismutase and TxA2 inhibitor U 63557A.
Attenuated coronary relaxation after reperfusion: effects of superoxide dismutase and TxA2 inhibitor U 63557A.
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再灌注后冠状动脉舒张减弱：超氧化物歧化酶和 TxA2 抑制剂 U 63557A 的作用。
DOI：
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发表时间：
1989
影响因子：
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通讯作者：
W. Nichols
中科院分区：
文献类型：
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作者：
J. Mehta;D. Lawson;W. Nichols
先前的研究表明内皮依赖性白三烯D4（LTD4）诱导的犬冠状动脉环舒张在体外。我们现在表明，冠状动脉闭塞后再灌注减弱（P <0.01）的松弛犬冠状动脉环响应LTD4以及乙酰胆碱（ACh），这表明内皮依赖性冠状动脉反应性的损失（n = 6只狗）。由于超氧阴离子已被证明会导致内皮源性舒张因子（EDRF）的分解，我们想知道用超氧阴离子清除剂超氧化物歧化酶（SOD）治疗狗是否会调节LTD4和ACh对再灌注冠状动脉环的影响。事实上，在冠状动脉再灌注前用SOD治疗犬（n = 5）导致LTD4和ACh诱导的冠状动脉环松弛得以保留。在冠状动脉再灌注前用选择性血栓素合成酶阻断剂U 63557A治疗另外五只狗也导致对LTD 4和ACh的反应的冠状动脉环松弛的保留。为了确定U 63557A诱导的冠状动脉反应性保留的机制，测量了U 63557A存在下犬中性粒细胞超氧阴离子的产生。虽然U 63557A对中性粒细胞中的超氧阴离子生成没有影响，但在存在血小板的情况下，它显著（P <0.02）抑制中性粒细胞中的超氧阴离子生成，最有可能是通过将血小板中积累的环内过氧化物分流到前列环素的形成，从而抑制中性粒细胞超氧阴离子的生成。因此，SOD和U 63557A保护LTD4和ACh在冠状动脉闭塞和再灌注后内皮介导的血管舒张的损失。
Previous studies demonstrate endothelium-dependent leukotriene D4 (LTD4)-induced relaxation of canine coronary arterial rings in vitro. We now show that coronary occlusion followed by reperfusion attenuates (P less than 0.01) the relaxation of canine coronary artery rings in response to LTD4 as well as acetylcholine (ACh), suggesting loss of endothelium-dependent coronary reactivity (n = 6 dogs). Since superoxide anions have been shown to cause breakdown of endothelium-derived relaxing factor (EDRF), we wondered whether treatment of dogs with superoxide anion scavenger superoxide dismutase (SOD) would modulate the effects of LTD4 and ACh on reperfused coronary artery rings. Indeed, treatment of dogs (n = 5) with SOD before coronary reperfusion resulted in preservation of LTD4- and ACh-induced relaxation of coronary rings. Treatment of another five dogs with selective thromboxane-synthetase blocker U 63557A before coronary reperfusion also resulted in preservation of coronary ring relaxation in response to LTD4 and ACh. To determine the mechanism of U 63557A-induced preservation of coronary reactivity, canine neutrophil superoxide anion generation in the presence of U 63557A was measured. Although U 63557A had no effect on superoxide anion generation in neutrophils alone, it markedly (P less than 0.02) inhibited superoxide anion generation in neutrophils in the presence of platelets, most likely via shunting of accumulated cyclic endoperoxide in platelets toward formation of prostacyclin, which inhibits neutrophil superoxide anion production. Thus SOD and U 63557A protect against loss of endothelium-mediated vascular relaxation by LTD4 and ACh after coronary occlusion and reperfusion.