Nitrite-induced improved blood circulation associated with an increase in a pool of RBC-NO with no bioactivity
Open accessAbstract
The reduction of nitrite by RBCs producing NO can play a role in regulating vascular tone. This hypothesis was investigated in rats by measuring the effect of nitrite infusion on mean arterial blood pressure (MAP), cerebral blood flow (CBF) and cerebrovascular resistance (CVR) in conjunction with the accumulation of RBC-NO. The nitrite infusion reversed the increase in MAP and decrease in CBF produced by L-NAME inhibition of e-NOS. At the same time there was a dramatic increase in RBC-NO. Correlations of RBC-NO for individual rats support a role for the regulation of vascular tone by this pool of NO. Furthermore, data obtained prior to treatment with L-NAME or nitrite are consistent with a contribution of RBC reduced nitrite in regulating vascular tone even under normal conditions. The role of the RBC in delivering NO to the vasculature was explained by the accumulation of a pool of bioactive NO in the RBC when nitrite is reduced by deoxygenated hemoglobin chains. A comparison of R and T state hemoglobin demonstrated a potential mechanism for the release of this NO in the T-state present at reduced oxygen pressures when blood enters the microcirculation. Coupled with enhanced hemoglobin binding to the membrane under these conditions the NO can be released to the vasculature.
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In vivo administration of nitrite via direct infusion, dietary supplementation, or its two-electron oxidized precursor nitrate leads to a decrease in blood pressure in normal and hypertensive patients with a concomitant increase in markers of NO formation.
“in vivo administration of nitrite either via direct infusion [25, 37, 83], dietary supplementation [84-86] or in the form of its two-electron oxidized precursor nitrate [87-89] leads to a decrease in blood pressure in normal and hypertensive patients with a concomitant increase in markers of NO formation”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [37]
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Lysenkov, S. P., & Muzhenya, D. V. (2026) · Сибирский научный медицинский журнал · doi:10.18699/ssmj20260301
- Authors
- Rifkind, J. M., Nagababu, E., Cao, Z., Barbiro-Michaely, E., & Mayevsky, A.
- Affiliations
- National Institutes of Health (US)
- National Institute on Aging (US)
- Bar-Ilan University (IL)
- Corresponding author
- Rifkind, Joseph M.
- ORCID
- Cao, Zeling
- Venue
- Advances in experimental medicine and biology
- Publisher
- Springer US
- Published
- 2009
- Volume
- 645
- Pages
- 27-34
- ISSN
- 0065-2598 (ISSN-L)
- PMC
- PMC2664541
- OpenAlex
- W2159360046
- Cited by
- 10
- References
- 15
- Citations by year
- 2026: 1 · 2017: 1 · 2016: 1 · 2014: 1
- FWCI
- 7.23
- Type
- book chapter
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Advances in experimental medicine and biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (Z01AG000433)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Keywords
- nitrite, nitric oxide, erythrocytes, nitrite reduction, vascular tone, cerebral blood flow, cerebrovascular resistance, mean arterial pressure, L-NAME, eNOS inhibition, deoxyhemoglobin, microcirculation
- MeSH terms
- Animals, Blood Circulation, Erythrocytes, Male, Nitric Oxide, Nitrites, Rats, Wistar, Rats
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