Hemoglobin mediated nitrite activation of soluble guanylyl cyclase
Abstract
Nitrite has long been known to be vasoactive when present at large concentrations but it was thought to be inactive under physiological conditions. Surprisingly, we have recently shown that supraphysiological and near physiological concentrations of nitrite cause vasodilation in the human circulation. These effects appeared to result from reduction of nitrite by deoxygenated hemoglobin. Thus, nitrite was proposed to play a role in hypoxic vasodilation. We now discuss these results in the context of nitrite reacting with hemoglobin and effecting vasodilation and present new data modeling the nitric oxide (NO) export from the red blood cell and measurements of soluble guanylate cyclase (sGC) activation. We conclude that NO generated within the interior of the red blood cell is not likely to be effectively exported directly as nitric oxide. Thus, an intermediate species must be formed by the nitrite/deoxyhemoglobin reaction that escapes the red cell and effects vasodilation.
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Several proposed mechanisms explain how nitrite-derived bioactivity can be exported from the red blood cell, generally involving either a compartment model with submembrane localization or formation of another nitrogen oxide such as a nitrosothiol or N2O3.
“Several proposed mechanisms have been constructed to explain how nitrite-derived bioactivity can be exported from the red blood cell and these generally involve either a compartment model with submembrane localization of the reaction allowing for inefficient free NO escape, or the formation of another nitrogen oxide such as a nitrosothiol or N2O3 that can get out of the red blood cell and carry NO”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [45]
Formation of N2O3 from nitrite would facilitate export of NO activity from the red blood cell and evidence for the formation of this species has been reported.
“Formation of N2O3 from nitrite would facilitate export of NO activity from the red blood cell and evidence for the formation of this species has been reported [45–47, 99].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [45]
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- Authors
- Jeffers, A., Xu, X., Huang, K. T., Cho, M., Hogg, N., Patel, R. P., & Kim-Shapiro, D. B.
- Affiliations
- Wake Forest University (US)
- Medical College of Wisconsin (US)
- University of Alabama at Birmingham (US)
- Venue
- Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology
- Publisher
- Elsevier BV
- Published
- 2005-10
- Volume
- 142
- Issue
- 2
- Pages
- 130-135
- ISSN
- 1095-6433 (ISSN-L)
- OpenAlex
- W1986272386
- Cited by
- 67
- References
- 24
- Citations by year
- 2021: 1 · 2020: 1 · 2019: 1 · 2018: 3 · 2017: 4 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 4 · 2012: 4
- FWCI
- 3.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL070146, HL58091, HL 70146, R01HL058091)
- National Institute of General Medical Sciences (GM55792)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Keywords
- nitrite, hemoglobin, soluble guanylate cyclase, nitric oxide, hypoxic vasodilation, erythrocytes, nitrite reduction, vasodilation
- MeSH terms
- Soluble Guanylyl Cyclase, Cyclic AMP, Animals, Biological Assay, Cell Line, Computer Simulation, Diffusion, Enzyme Activation, Erythrocytes, Cyclic GMP, Guanylate Cyclase, Hemoglobins, Humans, Immunoenzyme Techniques, Insecta, Models, Biological, Models, Chemical, Nitric Oxide, Nitrites, Vasodilation, Receptors, Cytoplasmic and Nuclear
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