Document Detail

Superoxide-lowering therapy with TEMPOL reverses arterial dysfunction with aging in mice.
MedLine Citation:
PMID:  22168264     Owner:  NLM     Status:  MEDLINE    
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.
Bradley S Fleenor; Douglas R Seals; Melanie L Zigler; Amy L Sindler
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-01-19
Journal Detail:
Title:  Aging cell     Volume:  11     ISSN:  1474-9726     ISO Abbreviation:  Aging Cell     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-03-16     Completed Date:  2012-06-08     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  101130839     Medline TA:  Aging Cell     Country:  England    
Other Details:
Languages:  eng     Pagination:  269-76     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.
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MeSH Terms
Antioxidants / therapeutic use*
Collagen / metabolism
Cyclic N-Oxides / therapeutic use*
NADPH Oxidase / metabolism
Oxidative Stress
Spin Labels
Superoxides / metabolism*
Vascular Diseases / drug therapy*
Grant Support
AG000279/AG/NIA NIH HHS; AG013038/AG/NIA NIH HHS; HL007822/HL/NHLBI NIH HHS; HL107120/HL/NHLBI NIH HHS; R01 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/AG/NIA NIH HHS; T32 AG000279-10/AG/NIA NIH HHS; T32 HL007822-14/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Antioxidants; 0/Cyclic N-Oxides; 0/Spin Labels; 11062-77-4/Superoxides; 2226-96-2/tempol; 9007-34-5/Collagen; EC Oxidase

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