The DOI matches its Crossref record; 116 of the 116 references it cites were found in a registry or an index.
Role of the anion nitrite in ischemia-reperfusion cytoprotection and therapeutics
Open accessAbstract
The anion nitrite (NO(2)(-)) constitutes a biochemical reservoir for nitric oxide (NO). Nitrite reduction to NO may be catalyzed by hemoglobin, myoglobin or other metal-containing enzymes and occurs at increasing rates under conditions of physiologic hypoxia or ischemia. A number of laboratories have now demonstrated in animal models the ability of nitrite to provide potent cytoprotection following focal ischemia-reperfusion (IR) injury of the heart, liver, brain, and kidney. While the mechanism of nitrite-mediated cytoprotection remains to be fully characterized, the release of nitrite-derived NO following IR appears to be central to this mechanism. The evidence of nitrite-mediated cytoprotection against IR injury in multiple animal models opens the door to potential therapeutic opportunities in human disease. Here we review the mechanisms for nitrite formation in blood and tissue, its metabolic equilibrium with NO, nitrate, and NO-modified proteins, the evidence supporting nitrite-mediated cytoprotection, and the potential mechanisms driving cytoprotection, and we explore the opportunities for the therapeutic application of nitrite for human disease.
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In the citing paper
“Nitrite administered before or during cardiac ischemia has been shown to protect cardiac function and attenuate infarct size in a number of small and large animal models (226, 374, 864).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [226]
In the citing paper
“Nitrite is a dietary constituent that protects the heart against I/R injury in many animal models during both ischemia and preconditioning stage [186,187,188,189,190,191,192].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [189]
In the citing paper
“relevant biological effects were associated with nitrite or nitrate, including beneficial effects against ischemia-reperfusion injury [11,18,19], vasorelaxant properties [20], pulmonary vasodilator effects [21][22][23], and antihypertensive effects in experimental [24][25][26][27] and in clinical studies [28][29][30].”
From Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension (2011) · cites this paper as [19]
Citations
Cites
Thornberry, N. A., & Lazebnik, Y. A. (1998) · Science · doi:10.1126/science.281.5381.1312 · Cited by 6,857
Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor
Gryglewski, R. J., Palmer, R. M. J., & Moncada, S. (1986) · Nature · doi:10.1038/320454a0 · Cited by 2,400
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
Self-citationCleeter, M. W. J., Cooper, J. M., Darley-Usmar, V. M., Moncada, S., & Schapira, A. H. V. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)00424-2 · Cited by 1,241
Direct measurement of free radical generation following reperfusion of ischemic myocardium.
Zweier, J. L., Flaherty, J. T., & Weisfeldt, M. L. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.5.1404 · Cited by 1,189
Brown, G. C., & Cooper, C. E. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)01290-3 · Cited by 1,055
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
The biological lifetime of nitric oxide: Implications for the perivascular dynamics of NO and O 2
Thomas, D. D., Liu, X., Kantrow, S. P., & Lancaster, J. R. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.1.355 · Cited by 760
Fas-Induced Caspase Denitrosylation
Mannick, J. B., Hausladen, A., Liu, L., Hess, D. T., Zeng, M., Miao, Q., Kane, L. S., Gow, A. J., & Stamler, J. S. (1999) · Science · doi:10.1126/science.284.5414.651 · Cited by 743
Poderoso, J. J., Carreras, M. C., Lisdero, C., Riobó, N., Schöpfer, F., & Boveris, A. (1996) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1996.0146 · Cited by 726
Cited by
Sorted by citations
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
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
“For example, it is possible that the protective effect of NO2 on infarct size that has been reported in experimental models of myocardial ischemia (20, 63, 73) might be due to an NO-mediated reduction in the energy (and O2) cost of contraction rather than, or perhaps in addition to, enhanced perfusion of ischemic area…”
BackgroundSources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
Tejero, J., Shiva, S., & Gladwin, M. T. (2019) · Physiological Reviews · doi:10.1152/physrev.00036.2017 · Cited by 541
Self-citationNitrite as Regulator of Hypoxic Signaling in Mammalian Physiology
van Faassen, E. E., Bahrami, S., Feelisch, M., Hogg, N., Kelm, M., Kim‐Shapiro, D. B., Kozlov, A. V., Li, H., Lundberg, J. O., Mason, R., et al. (2009) · Medicinal Research Reviews · doi:10.1002/med.20151 · Cited by 435
“4 nitrite seems inert under normoxic conditions, but starts to act as a source of NO if oxygen levels in the tissue drop below a certain threshold.(10,11) Various mechanisms for nitrite reduction have now been identified.”
BackgroundSelf-citationLansley, K. E., Winyard, P. G., Fulford, J., Vanhatalo, A., Bailey, S. J., Blackwell, J. R., DiMenna, F. J., Gilchrist, M., Benjamin, N., & Jones, A. M. (2011) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01070.2010 · Cited by 404
“Systolic and diastolic blood pressure were unchanged during PL supplementation, suggesting that the reduction in systolic blood pressure with NO3 -rich BR was mediated through the systemic reduction of NO3 -derived NO2 to NO (6, 11, 18).”
Background
Metadata
- Authors
- DEZFULIAN, C., RAAT, N., SHIVA, S., & GLADWIN, M.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- GLADWIN, M
- Venue
- Cardiovascular Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-07-15
- Volume
- 75
- Issue
- 2
- Pages
- 327-338
- ISSN
- 0008-6363 (ISSN-L)
- PMC
- PMC2002522
- OpenAlex
- W2128346933
- Cited by
- 198
- References
- 115
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 6 · 2022: 2 · 2021: 6 · 2020: 3 · 2019: 4 · 2018: 8 · 2017: 10 · 2016: 11 · 2015: 12 · 2014: 15 · 2013: 15 · 2012: 21
- FWCI
- 12.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cardiovascular Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99CL999999)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Ischemia and Reperfusion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Keywords
- nitrite, nitric oxide, ischemia-reperfusion injury, cytoprotection, nitrite reduction, nitrate, hypoxia, heart, liver, brain, kidney
- MeSH terms
- Animals, Anions, Humans, Nitric Oxide, Nitrites, Signal Transduction, Reperfusion Injury, Cytoprotection, Models, Animal, Muscle Cells
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