title: Role of extracellular superoxide dismutase in the mouse angiotensin slow pressor response.
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 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.
authors.affiliation: Cardiovascular-Kidney Institute and Division of Nephrology and Hypertension, Georgetown University, Washington, DC, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Welch
authors.forename: Tinatin
authors.initials: T
authors.lastname: Chabrashvili
authors.forename: Glenn
authors.initials: G
authors.lastname: Solis
authors.forename: Yifan
authors.initials: Y
authors.lastname: Chen
authors.forename: Pritmohinder S
authors.initials: PS
authors.lastname: Gill
authors.forename: Shakil
authors.initials: S
authors.lastname: Aslam
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Ji
authors.forename: Kathryn
authors.initials: K
authors.lastname: Sandberg
authors.forename: Pedro
authors.initials: P
authors.lastname: Jose
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Wilcox
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000235:genetics; D005110:Extracellular Space / Q000201:enzymology*; D007672:Kidney Cortex / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000378:metabolism; D020033:Protein Isoforms / Q000502:physiology; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013599:Systole / Q000187:drug effects / Q000235:genetics
chemical_list: D020033:Protein Isoforms; D000804:Angiotensin II; D013482:Superoxide Dismutase; D019255:NADPH Oxidases