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(Hypertension. 2006;48:934.)
© 2006 American Heart Association, Inc.

Original Articles

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

William J. Welch; Tinatin Chabrashvili; Glenn Solis; Yifan Chen; Pritmohinder S. Gill; Shakil Aslam; Xiaoyan Wang; Hong Ji; Kathryn Sandberg; Pedro Jose; Christopher S. Wilcox

From the Cardiovascular-Kidney Institute and Division of Nephrology and Hypertension (W.J.W., T.C., G.S., Y.C., P.S.G., S.A., H.J., K.S., C.S.W.) and Department of Pediatrics (X.W., P.J.), Georgetown University, Washington, DC.

Correspondence to Christopher S. Wilcox, Georgetown University Medical Center, PHC F6003, 3800 Reservoir Rd, NW, Washington, DC 20007. E-mail wilcoxch{at}georgetown.edu

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 p22^phox expression, and NADPH oxidase activity. Ang II infusion in EC-SOD +/+ mice significantly (P<0.05) increased MAP, RVR, p22^phox, 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 significant), RVR, NADPH oxidase activity, and lipid peroxidation. SOD activity in the kidneys of Ang II–infused mice was paradoxically higher in EC-SOD –/– mice (+/+: 8.8±1.2 U/mg protein^–1 versus –/–: 13.7±1.6 U/mg protein^–1; P<0.05) accompanied by a significant upregulation of mRNA and protein for Cu/Zn-SOD. In conclusion, EC-SOD protects normal mice against oxidative stress by attenuating renal p22^phox expression, NADPH oxidase activation, and the accompanying renal vasoconstriction and hypertension. However, during an Ang II slow pressor response, renal EC-SOD expression is reduced and, in its absence, renal Cu/Zn-SOD is upregulated and may prevent excessive Ang II–induced renal oxidative stress, renal vasoconstriction, and hypertension.

Key Words: oxidative stress • hypertension • renal • kidney • renal circulation • nitric oxide • endothelium

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