Blood Flow Regulation by S -Nitrosohemoglobin in the Physiological Oxygen Gradient
Abstract
The binding of oxygen to heme irons in hemoglobin promotes the binding of nitric oxide (NO) to cysteineβ93, forming S -nitrosohemoglobin. Deoxygenation is accompanied by an allosteric transition in S -nitrosohemoglobin [from the R (oxygenated) to the T (deoxygenated) structure] that releases the NO group. S -nitrosohemoglobin contracts blood vessels and decreases cerebral perfusion in the R structure and relaxes vessels to improve blood flow in the T structure. By thus sensing the physiological oxygen gradient in tissues, hemoglobin exploits conformation-associated changes in the position of cysteineβ93 SNO to bring local blood flow into line with oxygen requirements.
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Nitrite bioactivation is most prevalent during rapid deoxygenation, reaching a maximum conversion and nitric oxide-mediated effects at 50% oxygen bound hemoglobin.
“They showed that nitrite bioactivation is most prevalent during rapid deoxygenation, reaching a maximum conversion and nitric oxide-mediated effects at 50% oxygen bound hemoglobin.73,74”
From Nitrate-Nitrite-Nitric Oxide Pathway: Implications for Anesthesiology and Intensive Care (2010) · cites this paper as [74]
Other regulators of NOX4 include TNF-α, hypoxia, and PDGF.
“Other regulators include TNF-α (70, 681, 884, 1048), hypoxia (455), and PDGF (487).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [884]
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- Authors
- Stamler, J. S., Jia, L., Eu, J. P., McMahon, T. J., Demchenko, I. T., Bonaventura, J., Gernert, K., & Piantadosi, C. A.
- Affiliations
- Duke University (US)
- J. S. Stamler, Department of Medicine, Divisions of Respiratory and Cardiovascular Medicine and Department of Cell Biology, Duke University Medical Center, Room 321 MSRB, Box 2612, Durham, NC 27710, USA.
- Corresponding author
- Stamler, Jonathan S.
- Venue
- Science
- Published
- 1997-06-27
- Volume
- 276
- Issue
- 5321
- Pages
- 2034-2037
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2033240573
- Cited by
- 1,050
- References
- 0
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 20 · 2023: 16 · 2022: 22 · 2021: 20 · 2020: 17 · 2019: 16 · 2018: 23 · 2017: 20 · 2016: 24 · 2015: 26 · 2014: 16 · 2013: 27 · 2012: 40
- FWCI
- 24.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hl052529-05)
- National Heart, Lung, and Blood Institute (HR59130, HL 52529)
- 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
- S-nitrosohemoglobin, nitric oxide, hemoglobin, oxygen gradients, allosteric transition, blood flow regulation, vasodilation, vasoconstriction, cerebral perfusion, oxygen sensing
- MeSH terms
- Animals, Blood Pressure, Cerebrovascular Circulation, Cysteine, Hemodynamics, Hemoglobins, Mercaptoethanol, Models, Molecular, Nitric Oxide, Nitroso Compounds, Oxygen, Oxyhemoglobins, Protein Conformation, Rats, Sprague-Dawley, S-Nitrosothiols, Rats
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