The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.
Nitrite supplementation reverses vascular endothelial dysfunction and large elastic artery stiffness with aging: Sodium nitrite and vascular dysfunction with aging
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Pre-clinical studies with nitrate or nitrite also show the potential to protect against ischaemia-reperfusion injury and reduce arterial stiffness, inflammation and intimal thickness.”
From Vascular effects of dietary nitrate (as found in green leafy vegetables and beetroot) via the nitrate-nitrite-nitric oxide pathway (2013) · cites this paper as [150]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Thus, Sindler et al. found that nitrite reduced the elevated pulse wave velocity and levels of inflammatory cytokines IL-1b, IL6, INFg and TNFa [150].”
From Vascular effects of dietary nitrate (as found in green leafy vegetables and beetroot) via the nitrate-nitrite-nitric oxide pathway (2013) · cites this paper as [150]
The cited source says what the claim attributes to it.
In the citing paper
“Sindler et al. also detected depleted concentrations in the arteries and heart, which were restored to youthful levels (4-6 month controls) by 3 weeks' supplementation with sodium nitrite (50 mg l -1 in the drinking water) [150].”
From Vascular effects of dietary nitrate (as found in green leafy vegetables and beetroot) via the nitrate-nitrite-nitric oxide pathway (2013) · cites this paper as [150]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“While the efficacy of dietary NO 3 -to reduce systemic blood pressure in older age has been extensively studied (reviewed in 140; see also 139, 142), relatively few studies have assessed the effects of NO 3 -supplementation on exercise capacity in healthy older individuals.”
From Dietary Nitrate and Physical Performance (2018) · cites this paper as [142]
Experimental — accuracy not yet measuredIn the citing paper
“Oral supplementation with either nitrite or nitrate increases circulating nitrite levels and prevents and reverses endothelial dysfunction in a dose-dependent manner both in mice[68,69] and in healthy[70,71,97,111,112], hypertensive[113], and obese individuals[114], or in those with hypercholesterolemia[115] and peripheral arterial disease[116].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [69]
In the citing paper
“ameliorates endothelial dysfunction, as indicated by normalization of NO-mediated endothelium-dependent dilation.”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [171]
In the citing paper
“In old mice, short-term oral sodium nitrite supplementation reduces aortic pulse wave velocity, the gold-standard measure of large elastic artery stiffness”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [171]
In the citing paper
“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 [171]
In the citing paper
“vascular endothelial function as assessed by carotid artery EDD in response to acetylcholine, was impaired in old compared with young control animals (Fig. 4, top).”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [171]
In the citing paper
“Sodium nitrite treatment restored EDD in old mice by increasing NO-dependent dilation (Fig. 4, bottom).”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [171]
In the citing paper
“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 [171]
In the citing paper
“Nitrite concentrations in the plasma and large elastic arteries (aorta and carotid arteries) were lower in older animals, but sodium nitrite supplementation increased nitrite concentrations in the old mice up to or above those of young control animals (Fig. 2) (171).”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [171]
In the citing paper
“sodium nitrite had no effect on arterial function in the young mice in this study (171)”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [171]
In the citing paper
“aortic PWV was markedly higher (i.e., the aorta was stiffer) in old compared with young control mice (Fig. 3A).”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [171]
In the citing paper
“Sodium nitrite treatment normalized aortic nitrotyrosine staining in old mice, indicating amelioration of age-associated arterial oxidative stress.”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [171]
In the citing paper
“Sodium nitrite treatment reduced aortic PWV in old mice to well below old controls and not significantly different from that in young animals.”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [171]
In the citing paper
“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 [171]
In the citing paper
“Inhibition of NO using the NO synthase inhibitor l-NAME, markedly reduced EDD in young animals while having less effect in old mice, indicating that the impaired EDD in old animals was mediated by reduced NO bioavailability.”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [171]
In the citing paper
“Nitrite did not affect endothelium-independent dilation to sodium nitroprusside (171), indicating that the improvements in EDD were not induced by increased vascular smooth muscle sensitivity to NO.”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [171]
In the citing paper
“expression of the proinflammatory cytokines interleukin (IL)-1β, IL-6, interferon-γ, and tumor necrosis factor-α (TNF-α) were shown to be greater in aorta of old mice than young control mice (171)”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [171]
In the citing paper
“although it had no effect on EDD in old mice treated with sodium nitrite (171)”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [171]
In the citing paper
“The activity of the major antioxidant enzyme SOD was found to be ∼50% lower in aorta of old compared with young control mice”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [171]
In the citing paper
“Protein expression of NADPH oxidase was threefold greater in aorta of old mice compared with those of young control mice”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [171]
In the citing paper
“Inhibition of NADPH oxidase with apocynin had no effect on EDD in arteries of old animals treated with sodium nitrite”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [171]
In the citing paper
“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 [171]
In the citing paper
“Sepiapterin restored acetylcholine-induced EDD selectively in carotid arteries of old control mice”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [171]
In the citing paper
“TEMPOL had no effect on EDD in old mice treated with sodium nitrite”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [171]
In the citing paper
“but restored EDD in old control mice (171)”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [171]
In the citing paper
“short-term treatment with sodium nitrite restored SOD activity in aorta of old mice to levels observed in young controls”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [171]
In the citing paper
“but completely restored EDD in old control animals”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [171]
In the citing paper
“but this was normalized after sodium nitrite treatment”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [171]
In the citing paper
“Most importantly, nitrite supplementation completely reversed this age-associated arterial inflammation (171).”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [171]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology
Bedard, K., & Krause, K.-H. (2007) · Physiological Reviews · doi:10.1152/physrev.00044.2005 · Cited by 6,989
Heart Disease and Stroke Statistics—2010 Update: A Report From the American Heart Association
WRITING GROUP MEMBERS, Lloyd-Jones, D., Adams, R. J., Brown, T. M., Carnethon, M., Dai, S., De Simone, G., Ferguson, T. B., Ford, E., Furie, K., et al. (2010) · Circulation · doi:10.1161/circulationaha.109.192667 · Cited by 5,700
Prediction of Cardiovascular Events and All-Cause Mortality With Arterial Stiffness
Vlachopoulos, C., Aznaouridis, K., & Stefanadis, C. (2010) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2009.10.061 · Cited by 4,165
Lakatta, E. G., & Levy, D. (2003) · Circulation · doi:10.1161/01.cir.0000048892.83521.58 · Cited by 2,244
Arterial Stiffness and Cardiovascular Events: The Framingham Heart Study
Mitchell, G. F., Hwang, S.-J., Vasan, R. S., Larson, M. G., Pencina, M. J., Hamburg, N. M., Vita, J. A., Levy, D., & Benjamin, E. J. (2010) · Circulation · doi:10.1161/circulationaha.109.886655 · Cited by 2,225
Landmesser, U., Dikalov, S., Price, S. R., McCann, L., Fukai, T., Holland, S. M., Mitch, W. E., & Harrison, D. G. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200314172 · Cited by 1,660
Landmesser, U., Dikalov, S., Price, S. R., McCann, L. A., Fukai, T., Holland, S. M., Mitch, W. E., & Harrison, D. G. (2003) · Journal of Clinical Investigation · doi:10.1172/jci14172 · Cited by 1,652
Superoxide generation by endothelial nitric oxide synthase: The influence of cofactors
Vásquez-Vivar, J., Kalyanaraman, B., Martásek, P., Hogg, N., Masters, B. S. S., Karoui, H., Tordo, P., & Pritchard, K. A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.16.9220 · Cited by 1,484
Nitric oxide, oxidants, and protein tyrosine nitration
Radí, R. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307446101 · Cited by 1,477
Celermajer, D. S., Sørensen, K. E., Spiegelhalter, D. J., Georgakopoulos, D., Robinson, J. T. C., & Deanfield, J. E. (1994) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(94)90305-0 · Cited by 1,354
Cited by
Sorted by citations
Items 201–218 of 218
Nitrite and Nitrate as a Treatment for Hypertension
Kapil, V. (2017) · Springer eBooks · doi:10.1007/978-3-319-46189-2_17
Role of Autophagy in Age-Related Vascular Dysfunction
LaRocca, T. J. (2012) · CU Scholar (University of Colorado Boulder)
The efficacy of oral trehalose therapy to reverse age-associated vascular dysfunction in humans
Kaplan, R. E. (2015) · CU Scholar (University of Colorado Boulder)
The effect of dietary nitrates on vascular function and exercise capacity in chronic kidney disease
Ramick, M. G. (2024) · Library, Museums and Press - UDSpace (University of Delaware) · doi:10.58088/03xe-ca03
Izadi, F. (2018) · Research in Cardiovascular Medicine · doi:10.4103/rcm.rcm_14_17
Effect of dietary nitrate on sympathetic vasoconstriction in resting and contracting skeletal muscle
de Vries, C. J. (2015) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r3154f126
Insulin resistance and heart disease
Farooqui, A. A. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-819603-8.00003-1
Khalil, R. A. (2012) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.717967817.793467503
Jeddi, S., Yousefzadeh, N., Zarkesh, M., Kashfi, K., & Ghasemi, A. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1369379
Pharmacological treatments, mouse models, and the aorta
Humphrey, J. D. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95484-6.00021-x
Burrage, E. N., Coblentz, T., Prabhu, S. S., Eminhizer, N. M., Childers, R., Bryner, R. W., Lewis, S. E., Maxwell, B. A., DeVallance, E., Kelley, E. E., et al. (2025) · Experimental Physiology · doi:10.1113/ep092501
Idris-Khodja, N. (2012) · theses.fr (ABES) · doi:10.70675/b7dd5e95z7adbz45f4zb349z90e37c85791d
Ahmed, L. A., Al‐Massri, K. F., Hedya, S. A., & Abdelghany, T. M. (2026) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2026.179118
Chen, T., Ni, P., Li, M., Ma, H., Jin, D., Yu, Y., & Yu, R. (2026) · Frontiers in Nutrition · doi:10.3389/fnut.2026.1916253
Ferguson, S. K. (2015) · K-State Research Exchange (Kansas State University)
Metadata
- Authors
- Sindler, A. L., Fleenor, B. S., Calvert, J. W., Marshall, K. D., Zigler, M. L., Lefer, D. J., & Seals, D. R.
- Affiliations
- University of Colorado Boulder (US)
- Emory University (US)
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2011-03-31
- Volume
- 10
- Issue
- 3
- Pages
- 429-437
- ISSN
- 1474-9718 (ISSN-L)
- PMC
- PMC3094511
- OpenAlex
- W1559904992
- Cited by
- 218
- References
- 56
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 11 · 2023: 8 · 2022: 12 · 2021: 17 · 2020: 16 · 2019: 15 · 2018: 14 · 2017: 17 · 2016: 19 · 2015: 23 · 2014: 22 · 2013: 11 · 2012: 17
- FWCI
- 12.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (AG-000279, R37AG013038, R01AG013038, AG-013038, T32AG000279)
- National Heart, Lung, and Blood Institute (R01HL098481, HL007822, R01HL093579, T32HL007822, HL092141, R01HL092141, HL093579)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- nitrite supplementation, sodium nitrite, endothelial dysfunction, arterial stiffness, aging, nitric oxide bioavailability, oxidative stress, inflammation, NADPH oxidase, superoxide, tempol, apocynin, sepiapterin, pulse wave velocity, carotid artery, nitrotyrosine, inflammatory cytokines, arterial aging
- MeSH terms
- Acetophenones, Acetylcholine, Administration, Oral, Aging, Animals, Biopterins, Carotid Arteries, Cyclic N-Oxides, Elasticity, Endothelium, Vascular, Humans, Male, Myography, Nitric Oxide, Sodium Nitrite, Spin Labels, Superoxide Dismutase, Vasodilation, Vasodilator Agents, Cytokines, Oxidative Stress, NADPH Oxidases, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
