Role of Extracellular Superoxide Dismutase in the Mouse Angiotensin Slow Pressor Response

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Abstract
Low rates of angiotensin II (Ang II) infusion raise blood pressure, renal vascular resistance (RVR), NADPH oxidase activity, and superoxide. We tested the hypothesis that these effects are ameliorated by extracellular superoxide dismutase (EC-SOD). EC-SOD knockout (−/−) and wild type (+/+) mice were equipped with blood pressure telemeters and infused subcutaneously with Ang II (400 ng/kg per minute) or vehicle for 2 weeks. During vehicle infusion, EC-SOD −/− mice had significantly (P<0.05) higher MAP (+/+: 107±3 mm Hg versus −/−: 114±2 mm Hg; n=11 to 14), RVR, lipid peroxidation, renal cortical p22phox expression, and NADPH oxidase activity. Ang II infusion in EC-SOD +/+ mice significantly (P<0.05) increased MAP, RVR, p22phox, NADPH oxidase activity, and lipid peroxidation. Ang II reduced SOD activity in plasma, aorta, and kidney accompanied by reduced renal EC-SOD expression. During Ang II infusion, both groups had similar values for MAP (+/+ Ang II: 125±3 versus −/− Ang II: 124±3 mmHg; P value not signi...