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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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“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]
In the citing paper
“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]
In the citing paper
“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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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
Self-citationMethods to detect nitric oxide and its metabolites in biological samples
Bryan, N. S., & Grisham, M. B. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.04.026 · Cited by 1,005
Self-citationBailey, S. J., Fulford, J., Vanhatalo, A., Winyard, P. G., Blackwell, J. R., DiMenna, F. J., Wilkerson, D. P., Benjamin, N., & Jones, A. M. (2010) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00046.2010 · Cited by 607
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Nitric oxide synthesis and signalling in plants
Wilson, I. D., Neill, S. J., & Hancock, J. T. (2007) · Plant Cell & Environment · doi:10.1111/j.1365-3040.2007.01761.x · Cited by 493
Metadata
- 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 (medical) › 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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