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Therapeutic Uses of Inorganic Nitrite and Nitrate: From the Past to the Future
Open accessAbstract
Potential carcinogenic effects, blue baby syndrome, and occasional intoxications caused by nitrite, as well as the suspected health risks related to fertilizer overuse, contributed to the negative image that inorganic nitrite and nitrate have had for decades. Recent experimental studies related to the molecular interaction between nitrite and heme proteins in blood and tissues, the potential role of nitrite in hypoxic vasodilatation, and an unexpected protective action of nitrite against ischemia/reperfusion injury, however, paint a different picture and have led to a renewed interest in the physiological and pharmacological properties of nitrite and nitrate. The range of effects reported suggests that these simple oxyanions of nitrogen have a much richer profile of biological actions than hitherto assumed, and several efforts are currently underway to investigate possible beneficial effects in the clinical arena. We provide here a brief historical account of the medical uses of nitrite and nitrate over the centuries that may serve as a basis for a careful reassessment of the health implications of their exposure and intake and may inform investigations into their therapeutic potential in the future.
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“There is little doubt that the nitrite/sulfide interaction is of some biological relevance as nitrite is the most potent remedy known against sulfide poisoning [25].”
From On the chemical biology of the nitrite/sulfide interaction (2015) · cites this paper as [25]
In the citing paper
“This nitrate-nitrite-NO cycle offers a conceptually attractive explanation for the blood pressure lowering and cardioprotective effects of diets rich in nitrate and may provide the molecular basis for past and future therapeutic uses of nitrite/nitrate [20,25], although definitive chemical evidence for the significance of this pathway under physiological conditions is still lacking.”
From On the chemical biology of the nitrite/sulfide interaction (2015) · cites this paper as [25]
In the citing paper
“There is little doubt that the nitrite/sulfide interaction is of some biological relevance as nitrite is the most potent remedy known against sulfide poisoning [25].”
From On the chemical biology of the nitrite/sulfide interaction (2015) · cites this paper as [25]
In the citing paper
“This nitrate-nitrite-NO cycle offers a conceptually attractive explanation for the blood pressure lowering and cardioprotective effects of diets rich in nitrate and may provide the molecular basis for past and future therapeutic uses of nitrite/nitrate [20,25], although definitive chemical evidence for the significance of this pathway under physiological conditions is still lacking.”
From On the chemical biology of the nitrite/sulfide interaction (2015) · cites this paper as [25]
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Metadata
- Authors
- Butler, A. R., & Feelisch, M.
- Affiliations
- University of St Andrews (GB)
- ORCID
- Feelisch, Martin
- Venue
- Circulation
- Published
- 2008-04-22
- Volume
- 117
- Issue
- 16
- Pages
- 2151-2159
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2026713650
- Cited by
- 184
- References
- 96
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 8 · 2023: 4 · 2022: 12 · 2021: 8 · 2020: 7 · 2019: 10 · 2018: 6 · 2017: 10 · 2016: 13 · 2015: 18 · 2014: 17 · 2013: 10 · 2012: 15
- FWCI
- 8.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (acceptedVersion)
- Funders
- Medical Research Council
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Keywords
- inorganic nitrite, inorganic nitrate, therapeutic applications, heme proteins, ischemia-reperfusion injury, blue baby syndrome, nitrite toxicity, fertilizer overuse
- MeSH terms
- Cardiovascular Diseases, Humans, Nitrates, Nitrites, History, 15th Century, History, 16th Century, History, 17th Century, History, 18th Century, History, 19th Century, History, 20th Century, History, Ancient, History, Medieval
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 ›
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