Document Detail

Nitrite supplementation reverses vascular endothelial dysfunction and large elastic artery stiffness with aging.
MedLine Citation:
PMID:  21276184     Owner:  NLM     Status:  MEDLINE    
We tested the hypothesis that short-term nitrite therapy reverses vascular endothelial dysfunction and large elastic artery stiffening with aging, and reduces arterial oxidative stress and inflammation. Nitrite concentrations were lower (P < 0.05) in arteries, heart, and plasma of old (26-28 month) male C57BL6 control mice, and 3 weeks of sodium nitrite (50 mg L(-1) in drinking water) restored nitrite levels to or above young (4-6 month) controls. Isolated carotid arteries of old control mice had lower acetylcholine (ACh)-induced endothelium-dependent dilation (EDD) (71.7 ± 6.1% vs. 93.0 ± 2.0%) mediated by reduced nitric oxide (NO) bioavailability (P < 0.05 vs. young), and sodium nitrite restored EDD (95.5 ± 1.6%) by increasing NO bioavailability. 4-Hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL), a superoxide dismutase (SOD) mimetic, apocynin, a nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) inhibitor, and sepiapterin (exogenous tetrahydrobiopterin) each restored EDD to ACh in old control, but had no effect in old nitrite-supplemented mice. Old control mice had increased aortic pulse wave velocity (478 ± 16 vs. 332 ± 12 AU, P < 0.05 vs. young), which nitrite supplementation lowered (384 ± 27 AU). Nitrotyrosine, superoxide production, and expression of NADPH oxidase were ∼100-300% greater and SOD activity was ∼50% lower in old control mice (all P < 0.05 vs. young), but were ameliorated by sodium nitrite treatment. Inflammatory cytokines were markedly increased in old control mice (P < 0.05), but reduced to levels of young controls with nitrite supplementation. Short-term nitrite therapy reverses age-associated vascular endothelial dysfunction, large elastic artery stiffness, oxidative stress, and inflammation. Sodium nitrite may be a novel therapy for treating arterial aging in humans.
Amy L Sindler; Bradley S Fleenor; John W Calvert; Kurt D Marshall; Melanie L Zigler; David J Lefer; Douglas R Seals
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-03-31
Journal Detail:
Title:  Aging cell     Volume:  10     ISSN:  1474-9726     ISO Abbreviation:  Aging Cell     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-05-13     Completed Date:  2011-09-13     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  101130839     Medline TA:  Aging Cell     Country:  England    
Other Details:
Languages:  eng     Pagination:  429-37     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
Acetophenones / pharmacology
Acetylcholine / pharmacology*
Administration, Oral
Biopterin / analogs & derivatives,  pharmacology
Carotid Arteries / physiology*
Cyclic N-Oxides / pharmacology
Cytokines / biosynthesis
Elasticity / drug effects
Endothelium, Vascular / cytology,  drug effects*,  metabolism*
NADPH Oxidase / antagonists & inhibitors,  metabolism
Nitric Oxide / pharmacology
Oxidative Stress / drug effects
Sodium Nitrite / metabolism,  pharmacology*
Spin Labels
Superoxide Dismutase / metabolism,  pharmacology
Vasodilation / drug effects
Vasodilator Agents / pharmacology*
Grant Support
AG000279/AG/NIA NIH HHS; AG013038,/AG/NIA NIH HHS; HL007822/HL/NHLBI NIH HHS; HL092141/HL/NHLBI NIH HHS; HL093579/HL/NHLBI NIH HHS; HL098481-01/HL/NHLBI NIH HHS; R01 HL092141/HL/NHLBI NIH HHS; R01 HL092141-04/HL/NHLBI NIH HHS; R01 HL093579/HL/NHLBI NIH HHS; R01 HL093579-03/HL/NHLBI NIH HHS; R01 HL098481/HL/NHLBI NIH HHS; R01 HL098481-01/HL/NHLBI NIH HHS; R37 AG013038/AG/NIA NIH HHS; R37 AG013038-16/AG/NIA NIH HHS; T32 AG000279/AG/NIA NIH HHS; T32 AG000279-09/AG/NIA NIH HHS; T32 HL007822-13/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Acetophenones; 0/Cyclic N-Oxides; 0/Cytokines; 0/Spin Labels; 0/Vasodilator Agents; 17528-72-2/5,6,7,8-tetrahydrobiopterin; 22150-76-1/Biopterin; 2226-96-2/tempol; 31C4KY9ESH/Nitric Oxide; B6J7B9UDTR/acetovanillone; EC Dismutase; EC Oxidase; M0KG633D4F/Sodium Nitrite; N9YNS0M02X/Acetylcholine

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