Oxidative stress and vascular function: implications for pharmacologic treatments

Abstract

Production of considerable amounts of reactive oxygen species (ROS) eventually leads to oxidative stress. A key role of oxidative stress is evident in the pathologic mechanisms of endothelial dysfunction and associated cardiovascular diseases. Vascular enzymes such as NADPH oxidases, xanthine oxidase, and uncoupled endothelial nitric oxide synthase are involved in the production of ROS. The question remains whether pharmacologic approaches can effectively combat the excessive ROS production in the vasculature. Interestingly, existing registered cardiovascular drugs can directly or indirectly act as antioxidants, thereby preventing the damaging effects of ROS. Moreover, new compounds targeting NADPH oxidases have been developed. Finally, food-derived compounds appear to be effective inhibitors of oxidative stress and preserve vascular function.

Fig. 1

Molecular sources of vascular oxidative stress and pharmacologic intervention strategies. Vascular enzymes such as NADPH oxidase 2 (1), xanthine oxidase (2), and uncoupled endothelial nitric oxide synthase (3) can promote the production of reactive oxygen species (ROS) considerably. Eventually, these processes contribute to the development of endothelial dysfunction and vascular damage. Established and novel cardiovascular drugs, as well as dietary flavonoids, can attenuate cellular ROS concentrations via direct or indirect mechanisms. ACE—angiotensin-converting enzyme; Ang—angiotensin; AT₁—Ang II type 1; CaM—calmodulin; ET-1—endothelin 1; FAD—flavin adenine dinucleotide; FMN—flavin mononucleotide; L-Arg—l-arginine; L-Cit—l-citrulline; PDGF—platelet-derived growth factor; TGF-β—transforming growth factor-β