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Endothelial dysfunction is recognized as an in-dependent risk factor for the development of cardiovascular diseases, and is characterized by a reduced bioavailability of the antithrombotic and antiatherosclerotic autacoid NO (Davignon and Ganz, 2004). The decrease in NO is directly related to increased vascular oxidative stress, as O2 readily reacts with NO to form peroxyni-trite. Perhaps more importantly, the oxidative depletion of tetrahydrobiopterin causes the so-called uncoupling of endothelial NO syn-thase (eNOS), leading to the production of O2 instead of NO by the enzyme (Schulz et al., 2008). Despite the undisputed role of oxidative stress in the etiology of endothelial dysfunc-tion, large clinical trials with antioxidant ther-apies have failed to show a beneficial effect on cardiovascular outcome (Thomson et al., 2007). This discrepancy is probably explained at least in part by the formation of other reactive oxy-gen species from O2 that have more complex roles in intracellular signaling beyond NO scavenging. Several superoxide dismutases con-vert O2 to the more stable H2O2 that has widespread and more prolonged effects on endothelial cell function (for review see Cai, 2005). H2O2 is in turn eliminated through the actions of catalase and peroxidases. However, it is important to note that the exogenous ap-plication of catalase can ameliorate endothelial dysfunction in some models of hypertension (Ulker et al., 2003), whereas catalase aggra-vates the situation in models characterized by the uncoupling of eNOS (Landmesser et al., 2003). To date, several studies have reported that promoting the conversion of O2 to H2O2 to relieve NO scavenging does not prevent th