Nitrite in nitric oxide biology: Cause or consequence?
Abstract
All life requires nitrogen compounds. Nitrite is such a compound that is naturally occurring in nature and biology. Over the years, the pharmacological stance on nitrite has undergone a surprising metamorphosis, from a vilified substance that generates carcinogenic nitrosamines in the stomach to a life-saving drug that liberates a protective agent (nitric oxide or NO) during hypoxic events. Nitrite has been investigated as a vasodilator in mammals for over 125 years and is a known by-product of organic nitrate metabolism. There has been a recent rediscovery of some of the vasodilator actions of nitrite in physiology along with novel discoveries which render nitrite a fundamental molecule in biology. Until recently nitrite was thought to be an inert oxidative breakdown product of endogenous NO synthesis but the past few years have focused on the reduction of nitrite back to NO in the circulation as a possible mechanism for hypoxic vasodilatation. Nitrite has evolved into an endogenous signaling molecule and regulator of gene expression that may not only serve as a diagnostic marker but also find its role as a potential therapeutic agent of cardiovascular disease. These data therefore warrant a reevaluation on the fate and metabolism of nitrite in biological systems. This review serves to encompass the history and recent evolution of nitrite, the compartment-specific metabolism of nitrite and its role in plasma as a biomarker for disease, the role of nitrite as a potential regulator of NO homeostasis, and the future of nitrite-based research.
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Nitrate and nitrite can be reduced back to NO and other bioactive nitrogen oxides in vivo.
“However, it is now known that nitrate and nitrite can be reduced back to NO and other bioactive nitrogen oxides in vivo”
From Dietary Nitrate Supplementation and Exercise Performance (2014) · cites this paper as [2]
Body stores of nitrate and nitrite can be increased exogenously through the diet, particularly through consumption of green leafy vegetables.
“In addition to its generation by means of the NOS system, body stores of nitrate and nitrite may also be increased exogenously through the diet, particularly through the consumption of green leafy vegetables such as lettuce, spinach, rocket, celery, cress, and beetroot”
From Dietary Nitrate Supplementation and Exercise Performance (2014) · cites this paper as [2]
Inorganic nitrate is present in numerous foodstuffs and is abundant in green leafy vegetables and beetroot.
“Inorganic nitrate is present in numerous foodstuffs and is abundant in green leafy vegetables and beetroot.”
From Dietary Nitrate Supplementation and Exercise Performance (2014) · cites this paper as [2]
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Lefer, D. J. (2009) · Archives of Pharmacal Research · doi:10.1007/s12272-009-1804-y · Cited by 27 · see citing works
Cui, H., Feng, Y., Shu, C., Yuan, R., Bu, L., Jia, M., & Pang, B. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.01605 · Cited by 26 · see citing works
Nitric Oxide and its Metabolites in the Critical Phase of Illness: Rapid Biomarkers in the Making
Mian, A. I., Aranke, M., & Bryan, N. S. (2013) · The Open Biochemistry Journal · doi:10.2174/1874091x01307010024 · Cited by 26 · see citing works
Self-citationRey, J., Buffet, P. A., Cicéron, L., Milon, G., Mercereau‐Puijalon, O., & Safeukui, I. (2014) · Scientific Reports · doi:10.1038/srep03767 · Cited by 26 · see citing works
Heme proteins and oxidation in fresh and processed meats
Richards, M. P. (2010) · Elsevier eBooks · doi:10.1533/9780857090447.1.77 · Cited by 25 · see citing works
Ghasemi, A., Mehrazin, F., & Zahediasl, S. (2013) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-013-0251-x · Cited by 24 · see citing works
Absalan, G., Akhond, M., Bananejad, A., & Ershadifar, H. (2015) · Journal of the Iranian Chemical Society · doi:10.1007/s13738-015-0594-z · Cited by 25 · see citing works
- Authors
- Bryan, N. S.
- Affiliations
- The University of Texas Health Science Center at Houston (US)
- Corresponding author
- Bryan, Nathan S.
- ORCID
- Bryan, Nathan S.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2006-09
- Volume
- 41
- Issue
- 5
- Pages
- 691-701
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W99967797
- Cited by
- 260
- References
- 106
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 10 · 2023: 5 · 2022: 7 · 2021: 8 · 2020: 10 · 2019: 6 · 2018: 10 · 2017: 17 · 2016: 21 · 2015: 23 · 2014: 17 · 2013: 19 · 2012: 13
- FWCI
- 1.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- nitrite, nitric oxide, nitrite metabolism, nitrite reductase, nitric oxide homeostasis, cardiovascular disease treatment, nitrosamine formation
- MeSH terms
- Animals, Humans, Models, Biological, Models, Chemical, Nitrates, Nitric Oxide, Nitrites, Signal Transduction, Biomarkers, Nitric Acid
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