Journal article
Sex differences in protection against angiotensin II-induced endothelial dysfunction by manganese superoxide dismutase in the cerebral circulation
Hypertension (Dallas, Tex. 1979), Vol.55(4), pp.905-910
04/2010
DOI: 10.1161/HYPERTENSIONAHA.109.147041
PMCID: PMC2866174
PMID: 20194298
Abstract
Angiotensin II (Ang II) produces oxidative stress and endothelial dysfunction in blood vessels. The vasculature from females may be protected against deleterious effects of Ang II. We tested the hypothesis that manganese superoxide dismutase (MnSOD) protects against Ang II-induced endothelial dysfunction. Experiments were performed in C57Bl/6, wild-type (MnSOD(+/+)), and MnSOD-deficient (MnSOD(+/-)) mice treated systemically with vehicle or Ang II. Basilar arteries were isolated from mice treated for 1 week with a nonpressor dose of Ang II (0.28 mg/kg per day). Ang II treatment produced superoxide-mediated impairment of responses to the endothelium-dependent vasodilator acetylcholine (P<0.05). In male but not female MnSOD(+/+) mice, Ang II modestly inhibited responses to acetylcholine (P<0.05). In contrast, Ang II selectively impaired these responses by up to 70% in male MnSOD(+/-) mice (P<0.05), and this effect was reversed by Tempol (P<0.05). Ang II had no effect on acetylcholine responses in MnSOD(+/-) female mice. Vascular superoxide levels after treatment with an inhibitor of CuZn and extracellular superoxide dismutase were higher in Ang II-treated versus vehicle-treated MnSOD(+/-) mice. Thus, a nonpressor dose of Ang II produces endothelial dysfunction in male mice only, suggesting that the female vasculature is protected from Ang II. In male but not female mice, MnSOD deficiency enhanced endothelial dysfunction, suggesting that MnSOD normally protects the vasculature during disease states in which Ang II contributes to vascular dysfunction.
Details
- Title: Subtitle
- Sex differences in protection against angiotensin II-induced endothelial dysfunction by manganese superoxide dismutase in the cerebral circulation
- Creators
- Sophocles Chrissobolis - Department of Internal Medicine, Cardiovascular Center, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242-1081, USAFrank M Faraci
- Resource Type
- Journal article
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.55(4), pp.905-910
- Publisher
- United States
- DOI
- 10.1161/HYPERTENSIONAHA.109.147041
- PMID
- 20194298
- PMCID
- PMC2866174
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Grant note
- R01 HL038901 / NHLBI NIH HHS P01 NS024621 / NINDS NIH HHS P01 NS024621-22 / NINDS NIH HHS P01 HL062984-090001 / NHLBI NIH HHS R01 HL038901-21 / NHLBI NIH HHS HL-38901 / NHLBI NIH HHS NS-24621 / NINDS NIH HHS P01 HL062984 / NHLBI NIH HHS HL-62984 / NHLBI NIH HHS
- Language
- English
- Date published
- 04/2010
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040458602771
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