| Superoxide-lowering therapy with TEMPOL reverses arterial dysfunction with aging in mice. | |
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MedLine Citation:
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PMID: 22168264 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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To test the hypothesis that the antioxidant enzyme superoxide dismutase (SOD) mimetic TEMPOL improves arterial aging, young (Y, 4-6 mo) and old (O, 26-28 mo) male C57BL6 mice received regular or TEMPOL-supplemented (1mM) drinking water for 3 weeks (n=8/group). Aortic superoxide was 65% greater in O (p<0.05 vs. Y), which was normalized by TEMPOL. O had large elastic artery stiffening, as indicated by greater aortic pulse wave velocity (aPWV, 508 ± 22 vs. 418 ± 22 AU), which was associated with increased adventitial collagen I expression (p<0.05 vs. Y). TEMPOL reversed the age-associated increases in aPWV (434 ± 21 AU) and collagen in vivo, and SOD reversed increases in collagen I in adventitial fibroblasts from older rats in vitro. Isolated carotid arteries of O had impaired endothelial function as indicated by reduced acetylcholine-stimulated endothelium-dependent dilation (EDD) (75.6 ± 3.2 vs. 94.5 ± 2.0%) mediated by reduced nitric oxide (NO) bioavailability (L-NAME) associated with decreased endothelial NO synthase (eNOS) expression (p<0.05 vs. Y). TEMPOL restored EDD (94.5 ± 1.4%), NO bioavailability and eNOS in O. Nitrotyrosine and expression of NADPH oxidase were ∼100-200% greater, and MnSOD was ∼75% lower in O (p<0.05 vs. Y). TEMPOL normalized nitrotyrosine and NADPH oxidase in O, without affecting MnSOD. Aortic pro-inflammatory cytokines were greater in O (p<0.05 vs. Y) and normalized by TEMPOL. Short-term treatment of excessive superoxide with TEMPOL ameliorates large elastic artery stiffening and endothelial dysfunction with aging, and this is associated with normalization of arterial collagen I, eNOS, oxidative stress and inflammation. © 2011 The Authors Aging Cell© 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland. |
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Authors:
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Bradley S Fleenor; Douglas R Seals; Melanie L Zigler; Amy L Sindler |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-13 |
Journal Detail:
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Title: Aging cell Volume: - ISSN: 1474-9726 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-15 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101130839 Medline TA: Aging Cell Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2011 The Authors Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland. |
Affiliation:
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Department of Integrative Physiology, University of Colorado, Boulder, CO, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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