The DOI matches its Crossref record; 57 of the 58 references it cites were found in a registry or an index, and 1 are not checked yet.
Dietary nitrite restores NO homeostasis and is cardioprotective in endothelial nitric oxide synthase-deficient mice
Open accessAbstract
Endothelial production of nitric oxide (NO) is critical for vascular homeostasis. Nitrite and nitrate are formed endogenously by the stepwise oxidation of NO and have, for years, been regarded as inactive degradation products. As a result, both anions are routinely used as surrogate markers of NO production, with nitrite as a more sensitive marker. However, both nitrite and nitrate are derived from dietary sources. We sought to determine how exogenous nitrite affects steady-state concentrations of NO metabolites thought to originate from nitric oxide synthase (NOS)-derived NO as well as blood pressure and myocardial ischemia-reperfusion (I/R) injury. Mice deficient in endothelial nitric oxide synthase (eNOS-/-) demonstrated decreased blood and tissue nitrite, nitrate, and nitroso proteins, which were further reduced by low-nitrite (NOx) diet for 1 week. Nitrite supplementation (50 mg/L) in the drinking water for 1 week restored NO homeostasis in eNOS-/- mice and protected against I/R injury. Nitrite failed to alter heart rate or mean arterial blood pressure at the protective dose. These data demonstrate the significant influence of dietary nitrite intake on the maintenance of steady-state NO levels. Dietary nitrite and nitrate may serve as essential nutrients for optimal cardiovascular health and may provide a novel prevention/treatment modality for disease associated with NO insufficiency.
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“the nitrate/nitrite content of the fruits and vegetables could contribute to their cardiovascular health benefits in animals [29,33,78,79,80,81,82,83] and humans [31,84,85,86].”
From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [82]
In the citing paper
“pretreatment with this compound, delivered as a salt in the form of sodium nitrite, protects against ischemia/reperfusion (I/R) injury in the heart in preclinical models (7, 19, 20, 40, 46, 60, 79, 189).”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [20]
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“in vivo administration of nitrite either via direct infusion [25, 37, 83], dietary supplementation [84-86] or in the form of its two-electron oxidized precursor nitrate [87-89] leads to a decrease in blood pressure in normal and hypertensive patients with a concomitant increase in markers of NO formation”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [85]
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Citations
Cites
Vascular endothelial cells synthesize nitric oxide from L-arginine
Palmer, R. M. J., Ashton, D., & Moncada, S. (1988) · Nature · doi:10.1038/333664a0 · Cited by 4,786
The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics
Lundberg, J. O., Weitzberg, E., & Gladwin, M. T. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2466 · Cited by 2,739 · cited 1×
“confounding effects of nitrite and nitrate acting as NOS-independent sources of NO [9].”
BackgroundHypertension in mice lacking the gene for endothelial nitric oxide synthase
Huang, P. L., Huang, Z., Mashimo, H., Bloch, K. D., Moskowitz, M. A., Bevan, J. A., & Fishman, M. C. (1995) · Nature · doi:10.1038/377239a0 · Cited by 2,070
Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation
Cosby, K., Partovi, K. S., Crawford, J. H., Patel, R. P., Reiter, C. D., Martyr, S., Yang, B. K., Waclawiw, M. A., Zalos, G., Xu, X., et al. (2003) · Nature Medicine · doi:10.1038/nm954 · Cited by 1,807
Arnold, W. P., Mittal, C. K., Katsuki, S., & Murad, F. (1977) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.74.8.3203 · Cited by 1,459
Webb, A. J., Patel, N., Loukogeorgakis, S., Okorie, M., Aboud, Z., Misra, S., Rashid, R., Miall, P., Deanfield, J., Benjamin, N., et al. (2008) · Hypertension · doi:10.1161/hypertensionaha.107.103523 · Cited by 1,078
Workgroup Report: Drinking-Water Nitrate and Health—Recent Findings and Research Needs
Ward, M. H., de Kok, T. M. C. M., Levallois, P., Brender, J. D., Guliš, G., Nolan, B. T., & VanDerslice, J. A. (2005) · Environmental Health Perspectives · doi:10.1289/ehp.8043 · Cited by 924
Elevated blood pressures in mice lacking endothelial nitric oxide synthase
Shesely, E. G., Maeda, N., Kim, H.-S., Desai, K. M., Krege, J. H., Laubach, V. E., Sherman, P. A., Sessa, W. C., & Smithies, O. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.23.13176 · Cited by 908
Nitric Oxide: Pathophysiological Mechanisms
Gross, S. S., & Wolin, M. S. (1995) · Annual Review of Physiology · doi:10.1146/annurev.ph.57.030195.003513 · Cited by 888
Enzyme-independent formation of nitric oxide in biological tissues
Zweier, J. L., Wang, P., Samouilov, A., & Kuppusamy, P. (1995) · Nature Medicine · doi:10.1038/nm0895-804 · Cited by 788
Research works printed but not linked: 2
- Elrod, 2006, Cardiomyocyte-specific overexpression of NO synthase-3 protects against myocardial ischemia-reperfusion injury, Arterioscler. Thromb. Vasc. Biol., 26, 1517, 10.1161/01.ATV.0000224324.52466.e6 · DOI
- Zweier, 1995, Enzyme-independent formation of nitric oxide in biological tissues, Nat. Med., 1, 804, 10.1038/nm0895-804 · DOI · Paper page
Cited by
Sorted by citations
Food sources of nitrates and nitrites: The physiologic context for potential health benefits
Hord, N. G., Tang, Y., & Bryan, N. S. (2009) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.2008.27131 · Cited by 1,069
“Indeed, the Bryan laboratory has shown that nitrite can restore vascular tone after ischemia/reperfusion and substitutes for loss of eNOS-derived nitric oxide in eNOS-deficient mice (31, 32).”
BackgroundInfluentialSelf-citationMaia, L. B., & Moura, J. J. G. (2014) · Chemical Reviews · doi:10.1021/cr400518y · Cited by 401
Roles of dietary inorganic nitrate in cardiovascular health and disease
Lundberg, J. O., Carlström, M., Larsen, F. J., & Weitzberg, E. (2011) · Cardiovascular Research · doi:10.1093/cvr/cvq325 · Cited by 355
Lehnert, N., Kim, E., Dong, H. T., Harland, J. B., Hunt, A. P., Manickas, E. C., Oakley, K. M., Pham, J., Reed, G. C., & Alfaro, V. S. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00253 · Cited by 283
Hyde, E. R., Andrade, F., Vaksman, Z., Parthasarathy, K., Jiang, H., Parthasarathy, D. K., Torregrossa, A. C., Tribble, G., Kaplan, H. B., Petrosino, J. F., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0088645 · Cited by 275
“Numerous studies have shown that nitrite produced from bacterial nitrate reduction is an important storage pool for NO in blood and tissues when NOS-mediated NO production is insufficient [14,18,19,20,21].”
BackgroundSelf-citation
Metadata
- Authors
- Bryan, N. S., Calvert, J. W., Gundewar, S., & Lefer, D. J.
- Affiliations
- Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (US)
- Albert Einstein College of Medicine (US)
- Corresponding author
- Lefer, David J.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2008-08
- Volume
- 45
- Issue
- 4
- Pages
- 468-474
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC2662396
- OpenAlex
- W2074088550
- Cited by
- 161
- References
- 57
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 9 · 2023: 8 · 2022: 9 · 2021: 6 · 2020: 5 · 2019: 4 · 2018: 6 · 2017: 15 · 2016: 10 · 2015: 11 · 2014: 12 · 2013: 13 · 2012: 6
- FWCI
- 9.93
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Diabetes Association
- National Heart, Lung, and Blood Institute (R01HL093579, 2R01 HL-6049, R01HL060849)
- National Institute of Diabetes and Digestive and Kidney Diseases (F32DK077380)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Keywords
- dietary nitrite, nitric oxide homeostasis, endothelial nitric oxide synthase, nitrate, myocardial ischemia-reperfusion injury, cardioprotection, blood pressure, cardiovascular health, nitrite supplementation
- MeSH terms
- Animals, Diet, Homeostasis, Myocardium, Nitric Oxide, Nitrite Reductases, Nitrites, Mice, Knockout, Mice, Nitric Oxide Synthase Type III
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