Functional and analytical evidence for scavenging of oxygen radicals by L-arginine.
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 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) 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) 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.
Lass
Achim
A
Department of Pharmacology and Toxicology, Karl-Franzens-Universität Graz, Graz, Austria.
Suessenbacher
Astrid
A
Wölkart
Gerald
G
Mayer
Bernd
B
Brunner
Friedrich
F
D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use*; D001120:Arginine / Q000378:metabolism / Q000627:therapeutic use*; D003574:Cytochrome c Group / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D006335:Heart Injuries / Q000139:chemically induced / Q000517:prevention & control*; D008163:Luminescent Measurements; D008280:Magnetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000009:adverse effects* / Q000378:metabolism
D000975:Antioxidants; D003574:Cytochrome c Group; D017382:Reactive Oxygen Species; D001120:Arginine