Functional and Analytical Evidence for Scavenging of Oxygen Radicals by l-Arginine
- 1 May 2002
- journal article
- Published by Elsevier in Molecular Pharmacology
- Vol. 61 (5) , 1081-1088
Abstract
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). 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 asN G-nitro-l-arginine but not glycine, had similar cardioprotective effects indicated that the protection might be due to a direct chemical interaction ofl-arginine and its derivatives with oxygen radicals. In support, l-arginine and the derivatives prevented the formation of O⨪2 as determined by sensitive standard methods, whereas glycine did not. The radical scavenging activity ofl-arginine and derivatives was dose-dependent, with an apparent rate constant of approximately 4.8 × 103 M s−1 for the reaction of l-arginine with O⨪2 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.Keywords
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