© 2000 American Heart Association, Inc.
Editorials |
Physiological Effects of Peroxynitrite
Potential Products of the Environment
From the Cardiothoracic Research Laboratory, Division of Cardiothoracic Surgery, Carlyle Fraser Heart Center of Emory University, Atlanta, Ga.
Correspondence to Jakob Vinten-Johansen, PhD, Cardiothoracic Research Laboratory, Division of Cardiothoracic Surgery, Carlyle Fraser Heart Center of Emory University, 550 Peachtree St NE, Atlanta, GA 30365-2225. E-mail jvinten@emory.edu
Key Words: nitric oxide • cardioprotection • endothelium • contractile function
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Introduction |
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Peroxynitrite is a potent oxidant formed from the reaction between superoxide radicals and NO in a one-to-one stoichiometry. This reaction occurs at 6.7x109 mol/L-1 · s-1,1 and it is essentially irreversible because of its highly exothermic nature. Therefore, the reaction is diffusion-limited, and it out-competes the reaction of superoxide dismutase for superoxide radicals, which proceeds at a rate of 2x109 mol/L-1 · s-1. A key regulator of peroxynitrite production is the concentration of NO, and the reaction proceeds when the concentration of NO increases and can overcome dismutation by superoxide dismutase. This situation occurs when NO achieves micromolar concentrations as when there is a burst of NO production during ischemia/reperfusion and when NO is produced by cytokine-stimulated inducible NO synthase (iNOS) activity. The toxic effect of ONOO- and its protonated form, peroxynitrous acid, may stem from its oxidation of zinc fingers, protein thiols, membrane lipids, and iron and sulfur clusters of biological molecules. In addition, hydroxyl-like and nitrogen dioxide radicals are produced by homolytic cleavage, increasing the potential for oxidant-mediated tissue injury. Intermediates are also formed from the heterolytic cleavage of ONOO- to hydroxyl anion and nitronium ion (NO2+), catalyzed by the transition metal centers of superoxide dismutase and myeloperoxidase. The nitration of protein tyrosine residues gives rise to 3-nitrotyrosine, which is frequently used as an assay for ONOO- in tissues, blood, and perfusates.
Like NO, peroxynitrite has been associated with both deleterious and
beneficial effects. An advantage of the oxidant-mediated deleterious
effects
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