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Updated: Jul 14, 2026
Evaluation of Vascular Control Mechanisms Utilizing Video Microscopy of Isolated Resistance Arteries of Rats
Published on: December 5, 2017
NADPH oxidase contributes to vascular inflammation, insulin resistance, and remodeling in the transgenic (mRen2) rat
Yongzhong Wei1, Adam T Whaley-Connell, Kemin Chen
1University of Missouri-Columbia, Harry S. Truman VA Medical Center, Columbia, MO, USA.
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-alpha expression, apoptosis, and wall thickness, which were significantly attenuated by in vivo treatment with angiotensin type 1 receptor blockade (valsartan) or the superoxide dismutase/catalase mimetic (tempol). There was substantially diminished Akt and endothelial NO synthase activation in Ren2 aortas in response to in vivo insulin stimulation, and this was significantly improved by in vivo treatment with valsartan or tempol. In vivo treatment with valsartan, but not tempol, significantly reduced blood pressure in Ren2 rats. Further, there was reduced insulin induced Akt activation and increased tumor necrosis factor-alpha levels in vascular smooth muscle cells from Ren2 and Sprague-Dawley rats treated with angiotensin II, abnormalities that were abrogated by angiotensin type 1 receptor blockade with valsartan or antioxidant N-acetylcysteine. Collectively, these data suggest that increased angiotensin type 1 receptor/NADPH oxidase activation/reactive oxygen species contribute to vascular insulin resistance, endothelial dysfunction, apoptosis, and inflammation.
Insights
Elevated angiotensin II in rats worsens vascular insulin resistance and inflammation. Blocking the angiotensin type 1 receptor or using antioxidants improved insulin signaling and reduced vascular damage, highlighting a key pathway in metabolic dysfunction.
Area of Science:
- Vascular Biology
- Endocrinology
- Cardiovascular Research
Background:
- Reduced insulin sensitivity is linked to type 2 diabetes and hypertension.
- Angiotensin II impairs insulin actions in blood vessels, causing inflammation and dysfunction.
- Insulin normally promotes vasodilation and reduces inflammation.
Purpose of the Study:
- To investigate how angiotensin II affects insulin signaling, oxidative stress, and vascular health.
- To determine the role of NADPH oxidase and reactive oxygen species in angiotensin II-induced vascular damage.
- To evaluate the therapeutic potential of angiotensin type 1 receptor blockade and antioxidants.
Main Methods:
- Utilized transgenic Ren2 rats with elevated tissue angiotensin II levels.
- Administered angiotensin type 1 receptor blocker (valsartan) and antioxidant (tempol) in vivo.
- Assessed vascular inflammation, apoptosis, oxidative stress, and insulin signaling markers (Akt, eNOS).
- Examined insulin-induced Akt activation in vascular smooth muscle cells.
Main Results:
- Ren2 rats showed increased vascular oxidative stress, inflammation, apoptosis, and reduced insulin signaling.
- Valsartan and tempol attenuated these detrimental effects in Ren2 rats.
- Valsartan, but not tempol, reduced blood pressure in Ren2 rats.
- Angiotensin II impaired insulin signaling and increased inflammation in vascular cells, effects reversed by valsartan and N-acetylcysteine.
Conclusions:
- Increased angiotensin II signaling via the angiotensin type 1 receptor promotes vascular insulin resistance and inflammation.
- NADPH oxidase-derived reactive oxygen species are key mediators of this damage.
- Targeting the angiotensin type 1 receptor or oxidative stress may offer therapeutic strategies for vascular complications associated with insulin resistance.
