Oxidative stress plays an important role in the development of renal damage in diabetes and hypertension. The major source of oxidative stress is nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived superoxide anion (O2.-) that directly damage cell and also activate signaling of cell proliferation, adhesion molecules, and fibrosis. O2.- also inactivates endothelium derived nitric oxide and cause endothelial nitric oxide synthase uncoupling. In the spontaneously hypertensive rat and Dahl salt-sensitive hypertensive rat with heart failure and in the streptozotocininduced diabetic rats NADPH oxidase is increased via increased renal angiotensin II (AngII), and angiotensin converting enzyme inhibitor (ACEI) or AngII AT1 receptor blocker (ARB) confer renal protection by decrease in NADPH oxidase expression. Hypercholesterolemia additively increases NADPH oxidase in diabetes, as well as increases the adhesion molecule ICAM-1 and glomerular macrophage infiltration. Antioxidant drugs including apocynin, an inhibitor of the translocation of cytosolic components of NADPH oxidase, p38 MAPK inhibitor, or tempol, a superoxide dismutase mimetic, also show renoprotective effect in diabetes or in hypertension. In summary, stimulation of NADPH oxidase by renal AngII has a common pathogenic role in the development of renal damage in hypertension and diabetes and suppression of renal NADPH oxidase is a promising strategy against renal damage.
Keywords: nadph oxidase, hypertension, diabetes, kidney, angiotensin II, nitric oxide
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