Functional and analytical evidence for scavenging of oxygen radicals by L-arginine
Functional and analytical evidence for scavenging of oxygen radicals by L-arginine
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DOI：
10.1124/mol.61.5.1081
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发表时间：
2002-05-01
影响因子：
3.6
通讯作者：
Brunner, F
中科院分区：
文献类型：
--
作者：
Lass, A;Suessenbacher, A;Brunner, F
L-精氨酸是一氧化氮合酶的底物，已知在预防和治疗心血管疾病方面具有良好的作用。在动脉粥样硬化和缺血/再灌注等多种情况下，氧代谢物被认为可介导内皮和心肌损伤，L-精氨酸具有保护作用。在这里，我们研究了 L-精氨酸预防氧自由基诱导的心肌损伤的机制。缓冲液灌注的大鼠心脏受到电解产生的氧自由基或次黄嘌呤和黄嘌呤氧化酶的影响，产生超氧阴离子（O-2（条上的（中心点）））。两种来源的自由基都会损害心肌收缩力，而 L-精氨酸则可以防止这种损害。 D-精氨酸以及一氧化氮合酶抑制剂（例如 N-G-硝基-L-精氨酸，但不包括甘氨酸）具有类似的心脏保护作用，这表明这种保护作用可能是由于 L-精氨酸及其衍生物与氧自由基的直接化学相互作用所致。作为支持，L-精氨酸及其衍生物阻止了 O-2（条上的（中心点））的形成，如通过敏感的标准方法测定的那样，而甘氨酸则不然。 L-精氨酸及其衍生物的自由基清除活性呈剂量依赖性，通过使用 1-羟基-2,2,6,6-四甲基-4-氧代-哌啶 (TEMPONE-H) 作为自旋陷阱的电子顺磁共振波谱测定，L-精氨酸与 O-2（横条上的（中心点））反应的表观速率常数约为 4.8 x 10(3) M s(-1)。总之，本研究的结果证明了 L-精氨酸通过自由基清除对氧自由基诱导的心脏损伤具有保护作用。
L-Arginine, the substrate of nitric oxide synthase, is known to exert favorable effects in the prevention and treatment of cardiovascular diseases. In several conditions, including atherosclerosis and ischemia/reperfusion, where oxygen metabolites are thought to mediate endothelial and myocardial injury, L-arginine has protective effects. Here we studied the mechanisms by which L-arginine protects against oxygen radical-induced myocardial injury. Buffer-perfused rat hearts were subjected to oxygen radicals generated by electrolysis or to hypoxanthine and xanthine oxidase, which generates superoxide anions (O-2((center dot) over bar)). Both sources of radicals impaired myocardial contractility, whereas L-arginine prevented the impairment. The observation that D-arginine as well as nitric oxide synthase inhibitors, such as N-G-nitro-L-arginine but not glycine, had similar cardioprotective effects indicated that the protection might be due to a direct chemical interaction of L-arginine and its derivatives with oxygen radicals. In support, L-arginine and the derivatives prevented the formation of O-2((center dot) over bar) as determined by sensitive standard methods, whereas glycine did not. The radical scavenging activity of L- arginine and derivatives was dose-dependent, with an apparent rate constant of approximately 4.8 x 10(3) M s(-1) for the reaction of L-arginine with O-2((center dot) over bar) as determined by electron paramagnetic resonance spectroscopy using 1-hydroxy-2,2,6,6-tetramethyl-4-oxo-piperidine (TEMPONE-H) as spin trap. In summary, the results of this study demonstrate protective effects of L-arginine against oxygen radical-induced cardiac injury by free radical scavenging.