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Several pathologies of the cardiovascular system are associated with an augmented production of nitric oxide and/or superoxide-derived oxidants and/or alteration in the antioxidant detoxification pathways that lead to nitroxidative stress. One important consequence of these reactive intermediates at the biochemical level is the nitration of protein tyrosines, which is performed through either of two of the relevant nitration pathways that operate in vivo, namely peroxynitrite and heme peroxidase-dependent nitration. Proteins nitrated at tyrosine residues have been detected in several compartments of the cardiovascular system. In this review a selection of nitrated proteins in plasma (fibrinogen, plasmin, Apo-1), vessel wall (Apo-B, cyclooxygenase, prostaglandin synthase, Mn-superoxide dismutase) and myocardium (myofibrillar creatine kinase, alpha-actinin, sarcoplasmic reticulum Ca(2+) ATPase) are analyzed in the context of cardiovascular disease. Nitration of tyrosine can affect protein function, which could directly link nitroxidative stress to the molecular alterations found in disease. While some proteins are inactivated by nitration (e.g. Mn-SOD) others undergo a gain-of-function (e.g. fibrinogen) that can have an ample impact on the pathophysiology of the cardiovascular system. Nitrotyrosine is also emerging as a novel independent marker of cardiovascular disease. Pharmacological strategies directed towards inhibiting protein nitration will assist to shed light on the relevance of this post-translational modification to human cardiovascular pathology.

S-Nitrosothiols (RSNO) occur in vivo and have been proposed as nitric oxide ( ⅐ NO) storage and transport biomolecules. Still, the biochemical mechanisms by which RSNO release ⅐ NO in biological systems are not well defined, and in particular, the interactions between reactive oxygen species and RSNO have not been studied. In this work, we show that xanthine oxidase (XO), in the presence of purine (hypoxanthine, xanthine) or pteridine (lumazine) substrates, induces S-nitrosocysteine (CysNO) and S-nitrosoglutathione (GSNO) decomposition under aerobic conditions. (26,27). In this study, we evaluated the reaction between RSNO and O 2 . formed from the reaction catalyzed by xanthine oxidase (XO) (xanthine:oxygen oxidoreductase, EC 1.2.3.2) in the presence of purine or pteridine substrates and molecular oxygen (28). In vessel walls, where RSNO exerts signal-transducing actions, XO is present in high concentrations (29), and in human atherosclerotic arteries it impairs EDRF (endothelial derived relaxing factor) activity (29,30). Xanthine oxidase is composed of two identical subunits, each containing one atom of molybdenum, two iron-sulfur centers [Fe 2 S 2 ], and one FAD, which function as sequential redox groups in the intramolecular transfer of electrons (31). Since XO presents a relatively broad specificity for electron acceptor substrates, we also studied whether low molecular weight RSNO such as GSNO and CysNO could serve as XO substrates. We report herein that

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