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Protective role of manganese superoxide dismutase against angiotensin II‐induced, nox2‐dependent cerebral endothelial dysfunction
Author(s) -
Chrissobolis Sophocles,
Didion Sean P.,
Faraci Frank M.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1262-d
Subject(s) - nad(p)h oxidase , superoxide , superoxide dismutase , endothelial dysfunction , angiotensin ii , endocrinology , oxidative stress , medicine , reactive oxygen species , nadph oxidase , chemistry , nad+ kinase , acetylcholine , oxidase test , pharmacology , biochemistry , enzyme , receptor
Angiotensin II (Ang II)‐induced endothelial dysfunction may involve oxidative stress and NAD(P)H oxidase. Although mitochondria is a key source of superoxide, the role of superoxide dismutase (SOD) localized in mitochondria (MnSOD) in protecting against Ang II‐induced endothelial dysfunction is unknown. We tested if Ang II causes superoxide‐mediated endothelial dysfunction via nox2‐containing NAD(P)H oxidase, and if MnSOD protects against Ang II. Experiments were performed in cannulated, pressurized basilar artery segments from C57Bl/6, NAD(P)H oxidase (nox2) deficient, wild‐type (+/+) and MnSOD deficient (+/−) mice. In C57Bl/6, Ang II treatment using osmotic minipumps (7 days, 0.28 or 1.4 mg/kg/day) reduced vasodilation to acetylcholine (ACh) when compared to vehicle (P<0.05), that was partially restored by a superoxide scavenger, Tempol. In contrast to C57Bl/6, responses to ACh were not impaired in nox2 deficient mice treated with Ang II (P>0.05), suggesting Ang II‐induced vascular dysfunction is nox2‐dependent. In MnSOD +/+, Ang II inhibited ACh responses by ~40%, (P<0.05). In MnSOD +/−, Ang II treatment caused greater impairment of ACh responses (by ~55–85%; P<0.05). Ang II treatment did not impair responses to nitroprusside in any group. Thus, chronic Ang II causes nox2‐mediated endothelial dysfunction, and MnSOD may protect against Ang II‐induced cerebral endothelial dysfunction.