Therapeutic Uses of Inorganic Nitrite and Nitrate: From the Past to the Future

Butler, Anthony R.; Feelisch, Martin

doi:10.1161/circulationaha.107.753814

Cited by 185Nitric Oxide and Endothelin EffectsCardiovascular Health and Disease PreventionHemoglobin structure and function

Therapeutic Uses of Inorganic Nitrite and Nitrate: From the Past to the Future

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Butler, Anthony R., Feelisch, Martin·2008·Circulation

DOI 10.1161/circulationaha.107.753814

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Abstract

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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Nitrite is the most potent remedy known against sulfide poisoning.
“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]
Definitive chemical evidence for the significance of the nitrate-nitrite-NO pathway under physiological conditions is still lacking.
“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]
The nitrite/sulfide interaction is of some biological relevance.
“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]
The nitrate-nitrite-NO cycle offers a conceptually attractive explanation for the blood pressure lowering and cardioprotective effects of diets rich in nitrate.
“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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Authors: Butler, A. R., & Feelisch, M.
Affiliations: University of St Andrews (GB)
ORCID: Feelisch, Martin
Venue: Circulation
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2008-04-22
Volume: 117
Issue: 16
Pages: 2151-2159
ISSN: 0009-7322 (ISSN-L)
1524-4539
DOI: 10.1161/circulationaha.107.753814
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 › Nitric Oxide and Endothelin Effects
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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

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Therapeutic Uses of Inorganic Nitrite and Nitrate: From the Past to the Future

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