NADPH Oxidase Contributes to Vascular Inflammation, Insulin Resistance, and Remodeling in the Transgenic (mRen2) Rat

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Abstract
Reduced insulin sensitivity is characteristic of various pathological conditions such as type 2 diabetes mellitus and hypertension. Angiotensin II, acting through its angiotensin type 1 receptor, inhibits the actions of insulin in the vasculature which may lead to deleterious effects such as vascular inflammation, remodeling, endothelial dysfunction, and insulin resistance. In contrast, insulin normally exerts vasodilatory, antiinflammatory, and prosurvival actions. To explore the impact of angiotensin II on insulin signaling, NADPH oxidase–derived reactive oxygen species formation, vascular inflammation, apoptosis, and remodeling, we used transgenic TG(mRen2)27 (Ren2) rats, which harbor the mouse renin transgene and exhibits elevated tissue angiotensin II levels. Compared with Sprague-Dawley controls, Ren2 aortas exhibited greater NADPH oxidase activity, reactive oxygen species levels, C-reactive protein, tumor necrosis factor-α expression, apoptosis, and wall thickness, which were significantly attenuat...