Angiotensin II–Induced Reactive Oxygen Species and the Kidney

Redox Control of Renal Function and Hypertension

“…Anti-sense Nox1 mRNA completely inhibited Ang II-induced O 2 иϪ production, supporting a role for Nox1 in redox signaling in vascular smooth muscle cells. NAD(P)H oxidase, as well as other metabolic oxidases such as xanthine oxidase and mitochondrial respiratory chain enzymes (I-IV), are functional in the kidney (278). However, we and others have identified NAD(P)H oxidase-induced ROS production as a primary initiator of oxidative stress within the kidney (183,353,355,356 onists that bind to D1-like receptors, and to H ϩ fluxes (28,89,146,184,259,353,377,384) (Figs.…”

“…1 and Table 1). In the mitochondria, most of the O 2 иϪ is generated by leakage from the electron-transport chain (nonenzymatically produced by semiubiquinone) and the Krebs cycle (278). This constitutes 2% of all electron-transport chain by-products; the remaining 98% goes toward producing O 2 and H 2 O.…”

“…This constitutes 2% of all electron-transport chain by-products; the remaining 98% goes toward producing O 2 and H 2 O. In overall quantitative terms, mitochondrial electron-transport chain-generated O 2 иϪ may be the most important source (278). O 2 иϪ also is produced by metabolic oxidases, including nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase, xanthine oxidase (XO), P-450 monooxygenase, lipooxygenase (LOX), and cyclooxygenase (COX) (278) O 2) .…”

“…In overall quantitative terms, mitochondrial electron-transport chain-generated O 2 иϪ may be the most important source (278). O 2 иϪ also is produced by metabolic oxidases, including nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase, xanthine oxidase (XO), P-450 monooxygenase, lipooxygenase (LOX), and cyclooxygenase (COX) (278) O 2) . Excess O 2 иϪ also reduces transition metal ions such as Fe 3ϩ and Cu 2ϩ , the reduced forms of which, in turn, can react with H 2 O 2 to produce и OH (Fenton and Haber-Weiss reactions, respectively).…”

“…The enzyme complex better known as NAD(P)H oxidase is now well recognized as a major source of ROS production in vascular and renal cells (91,248). More important, it is the enzyme complex responsible for generating Ang II-mediated O 2 иϪ in the vast majority of cardiovascular diseases including hypertension (278). The structure and function of this enzyme complex have been extensively reviewed elsewhere (6).…”