Sodium nitrite de-stiffening of large elastic arteries with aging: Role of normalization of advanced glycation end-products
Open accessAbstract
We tested the hypothesis that sodium nitrite treatment reverses large elastic artery stiffening in old mice via reductions in collagen I, increases in elastin and/or decreases in advanced glycation end products (AGEs) mediated by reduced oxidative stress. Aortic pulse wave velocity (aPWV), a measure of large elastic artery stiffness, was greater in old (26-28months) compared with young (4-6months) control animals (520±9 vs. 405±6cm/s, p<0.05), and this was reversed by 3weeks of sodium nitrite treatment (50mg/L) (435±17cm/s). Age-related increases (p<0.05) in aortic superoxide production were associated with greater total and adventitial nitrotyrosine staining, all of which were reversed by nitrite treatment. Total and adventitial transforming growth factor β and collagen I were increased, and total and medial elastin were reduced with aging (p<0.05), but were unaffected by sodium nitrite. Aorta from old mice had increased total, adventitial and medial AGEs (p<0.05 vs. young), which were normalized by sodium nitrite treatment. In aortic segments from young mice in vitro, pyrogallol (10μM), a superoxide generator, induced an "aging-like" increase in AGEs, and direct treatment with AGEs induced vascular stiffening; these effects were prevented by incubation with sodium nitrite. De-stiffening of aged large elastic arteries by short-term sodium nitrite therapy is mediated in part by normalization of AGEs secondary to amelioration of oxidative stress.
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Improvements in age-related vascular dysfunction with nitrite are mediated by reductions in oxidative stress and inflammation.
“These improvements in age-related vascular dysfunction with nitrite are mediated by reductions in oxidative stress and inflammation”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [53]
Staining intensity for nitrotyrosine, a cellular marker of oxidant modification of proteins, was markedly greater in aorta of old compared with young control mice.
“the staining intensity for nitrotyrosine, a cellular marker of oxidant modification of proteins, was markedly greater in aorta of old compared with young control mice (53, 171) (Fig. 5A).”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [53]
Nitrite supplementation normalized total, adventitial, and medial advanced glycation end products in the aorta of old mice.
“nitrite supplementation normalized total, adventitial, and medial AGEs in the aorta of old mice (Fig. 3B).”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [53]
Superoxide production is much greater in aorta from old mice than from young control mice.
“Superoxide production was much greater in aorta from old compared with young control mice”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [53]
Short-term treatment with sodium nitrite completely normalizes superoxide formation in old animals.
“short-term treatment with sodium nitrite completely normalized superoxide formation in old animals (53, 171)”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [53]
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- Authors
- Fleenor, B. S., Sindler, A. L., Eng, J. S., Nair, D. P., Dodson, R. B., & Seals, D. R.
- Affiliations
- University of Colorado Boulder (US)
- Corresponding author
- Fleenor, Bradley S.
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 2012-08
- Volume
- 47
- Issue
- 8
- Pages
- 588-594
- ISSN
- 0531-5565 (ISSN-L)
- PMC
- PMC3389216
- OpenAlex
- W2060667937
- Cited by
- 85
- References
- 23
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 4 · 2022: 4 · 2021: 6 · 2020: 9 · 2019: 4 · 2018: 4 · 2017: 7 · 2016: 10 · 2015: 8 · 2014: 13 · 2013: 6 · 2012: 2
- FWCI
- 5.97
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Experimental Gerontology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (AG-000279, R37AG013038, R01AG013038, AG-013038, T32AG000279)
- National Heart, Lung, and Blood Institute (HL007822, T32HL007822)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Physical Sciences › Engineering › Biomedical Engineering › Elasticity and Material Modeling
- Keywords
- sodium nitrite, arterial stiffness, aging, advanced glycation end products, oxidative stress, superoxide, nitrotyrosine, type I collagen, elastin, TGF-beta, pulse wave velocity, aorta, pyrogallol, vascular aging
- MeSH terms
- Aging, Animals, Antioxidants, Aorta, Drug Evaluation, Preclinical, Elasticity, Elastin, Male, Pyrogallol, Sodium Nitrite, Superoxides, Tyrosine, Transforming Growth Factor beta, Glycation End Products, Advanced, Oxidative Stress, Collagen Type I, Tissue Culture Techniques, Mice, Vascular Stiffness
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