NO Generation From Nitrite and Its Role in Vascular Control
Abstract
NO generated from l-arginine by NO synthases (NOSs) in the endothelium and in other cells plays a central role in several aspects of vascular biology. The biological activity of NO is acutely terminated by oxidation to nitrite and nitrate, and these compounds have long been considered only as inert end-products of NO. However, this dogma is now being challenged because recent research convincingly has shown that the nitrite ion can be recycled back to bioactive NO again in blood and tissues. Nitrite reduction to NO can occur via several routes involving enzymes, proteins, vitamins, or even simple protons. This pathway may serve as a backup system for NO generation in conditions such as hypoxia, in which the NOS/l-arginine system is compromised, but detrimental effects can also be foreseen. With this new knowledge, nitrate and nitrite should probably be viewed as storage pools for NO rather than inert waste products. Here we discuss novel aspects of nitrite-dependent NO generation in vivo and its role in vascular control.
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The half-life of nitrate is 5-8 h, much longer than that of nitrite, which has been reported as 1-5 min ex vivo and ~20-45 min in vivo.
“The half-life of nitrate is 5-8 h [77,79,111,141,142], which is much longer than that of nitrite, which has been reported as being 1-5 min ex vivo [77,142] and ~20-45 min in vivo [86,112].”
From Vascular effects of dietary nitrate (as found in green leafy vegetables and beetroot) via the nitrate-nitrite-nitric oxide pathway (2013) · cites this paper as [142]
The half-lives table in “Nitrite Reduction to NO In Vivo” (page unavailable) lists 5–8 hours for nitrate and 1–5 minutes for nitrite, supporting the values attributed to this paper. It describes these as approximate blood/plasma values from human studies, however, and does not identify the 1–5-minute value as ex vivo. The separate 20–45-minute in vivo figure is cited to other sources in the citing sentence. (LLM, conf=0.84)
Experimental — accuracy not yet measuredNitrite as a reservoir can be further reduced to NO via numerous pathways in blood and tissue, and this process is accelerated under hypoxic conditions.
“Nitrite as a reservoir can be further reduced to NO via numerous pathways in blood and tissue, and this process is indeed accelerated under hypoxic conditions.44 -47”
From Dietary nitrate supplementation improves revascularization in chronic ischemia (2012) · cites this paper as [46]
NOS3 dependent NO production plays an important role in regulating steady state plasma nitrite levels, while also influencing nitrate, nitroso, and nitrosyl products in tissues.
“NOS3 dependent NO production plays an important role in regulating steady state plasma nitrite levels, while also influencing nitrate, nitroso, and nitrosyl products in tissues [72, 73].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [73]
Nitrite anion is recycled back to NO in multiple ways.
“However, now it is clear that nitrite anion is recycled back to NO in multiple ways.”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [73]
High concentrations of oxyhemoglobin usually found in the bloodstream can easily convert nitrite to nitrate.
“the high concentrations of oxyhemoglobin usually found in the bloodstream can easily convert nitrite to nitrate [47,48].”
From Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension (2011) · cites this paper as [47]
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References 99 · Cited by 341
Research works printed but not linked: 3
- Gladwin MT, Schechter AN. NO contest: nitrite versus S-nitroso- hemoglobin. Circ Res. 2004;94:851-855.
- Moncada S, Palmer RMJ, Higgs EA. Nitric oxide: physiology, patho- physiology, pharmacology. Pharmacol Rev. 1991;43:109 -141.
- Singel DJ, Stamler JS. Chemical physiology of blood flow regulation by red blood cells. Annu Rev Physiol. 2005;67:99 -145.
- Authors
- Lundberg, J. O., & Weitzberg, E.
- Affiliations
- Karolinska University Hospital (SE)
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2005-05
- Volume
- 25
- Issue
- 5
- Pages
- 915-922
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2132704929
- Cited by
- 341
- References
- 99
- Citations by year
- 2025: 6 · 2024: 9 · 2023: 8 · 2022: 9 · 2021: 12 · 2020: 10 · 2019: 10 · 2018: 13 · 2017: 14 · 2016: 14 · 2015: 19 · 2014: 16 · 2013: 14 · 2012: 29
- FWCI
- 3.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Hjärt-Lungfonden
- Vetenskapsrådet
- Ekhagastiftelsen
- 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 › Molecular Biology › Redox biology and oxidative stress
- Keywords
- nitrite, nitric oxide, nitrate, nitric oxide synthase, L-arginine, vascular regulation, hypoxia, nitrite reduction
- MeSH terms
- Animals, Endothelium, Vascular, Humans, Nitrates, Nitric Oxide, Nitrites, Vasodilation
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