Angiotensin II (Ang II)‐Induced Oxidative Stress and Endothelial Dysfunction in the Cerebral Circulation

Abstract

Hypertension (HT) has many deleterious effects on the cerebral circulation. Ang II, known to play a major role in HT, has been shown to increase vascular superoxide and produce endothelial dysfunction. Although mitochondria are a major source of superoxide, the role of superoxide dismutase localized in mitochondria (MnSOD) in protecting against Ang II-induced oxidative stress and endothelial dysfunction is unknown. The aims of this study were to test whether Ang II causes superoxide-mediated endothelial dysfunction and whether MnSOD protects against Ang II-induced endothelial dysfunction. Experiments were performed in cannulated, pressurized (60 mmHg) segments of isolated basilar artery from C57Bl/6, wild-type (MnSOD +/+) and MnSOD deficient (MnSOD +/−) mice. In C57Bl/6 mice, Ang II treatment (7 days) using osmotic minipumps (200 or 1000 ng/kg/min) caused dose-dependent impairment of vasodilatation to acetylcholine (ACh) when compared to vehicle treatment. For example, the maximum response to ACh was inhibited by ~30 and 55% by 200 and 1000 ng/kg/min Ang II, respectively (P<0.05). Vasodilatation to nitroprusside (NP) was unaffected by Ang II. In MnSOD +/+ mice, Ang II treatment (200 ng/kg/min) impaired ACh dilatation, and preliminary data suggests greater impairment of ACh responses in MnSOD +/− mice. Ang II treatment did not impair NP responses. Thus, Ang II impairs ACh responses in cerebral arteries and MnSOD may protect against Ang II-induced endothelial dysfunction.