| 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: MEDLINE |
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 months) and old (O, 26-28 months) male C57BL6 mice received regular or TEMPOL-supplemented (1mM) drinking water for 3 weeks (n = 8 per 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 the 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. |
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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; Research Support, N.I.H., Extramural Date: 2012-01-19 |
Journal Detail:
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Title: Aging cell Volume: 11 ISSN: 1474-9726 ISO Abbreviation: Aging Cell Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-03-16 Completed Date: 2012-06-08 Revised Date: 2013-04-03 |
Medline Journal Info:
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Nlm Unique ID: 101130839 Medline TA: Aging Cell Country: England |
Other Details:
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Languages: eng Pagination: 269-76 Citation Subset: IM |
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 80309, USA. bradley.fleenor@colorado.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aging* Animals Antioxidants / therapeutic use* Collagen / metabolism Cyclic N-Oxides / therapeutic use* Male Mice NADPH Oxidase / metabolism Oxidative Stress Rats Spin Labels Superoxides / metabolism* Vascular Diseases / drug therapy* |
| Grant Support | |
ID/Acronym/Agency:
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AG000279/AG/NIA NIH HHS; AG013038/AG/NIA NIH HHS; HL007822/HL/NHLBI NIH HHS; HL107120/HL/NHLBI NIH HHS; R01 HL107120-02/HL/NHLBI NIH HHS; R37 AG013038/AG/NIA NIH HHS; R37 AG013038-12/AG/NIA NIH HHS; T32 AG000279-10/AG/NIA NIH HHS; T32 HL007822-14/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antioxidants; 0/Cyclic N-Oxides; 0/Spin Labels; 11062-77-4/Superoxides; 2226-96-2/tempol; 9007-34-5/Collagen; EC 1.6.3.1/NADPH Oxidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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