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CHEMICAL PHYSIOLOGY OF BLOOD FLOW REGULATION BY RED BLOOD CELLS: The Role of Nitric Oxide and S-Nitrosohemoglobin
Abstract
▪ Abstract Blood flow in the microcirculation is regulated by physiological oxygen (O 2) gradients that are coupled to vasoconstriction or vasodilation, the domain of nitric oxide (NO) bioactivity. The mechanism by which the O 2 content of blood elicits NO signaling to regulate blood flow, however, is a major unanswered question in vascular biology. While the hemoglobin in red blood cells (RBCs) would appear to be an ideal sensor, conventional wisdom about its chemistry with NO poses a problem for understanding how it could elicit vasodilation. Experiments from several laboratories have, nevertheless, very recently established that RBCs provide a novel NO vasodilator activity in which hemoglobin acts as an O 2 sensor and O 2-responsive NO signal transducer, thereby regulating both peripheral and pulmonary vascular tone. This article reviews these studies, together with biochemical studies, that illuminate the complexity and adaptive responsiveness of NO reactions with hemoglobin. Evidence for the pivotal role of S-nitroso (SNO) hemoglobin in mediating this response is discussed. Collectively, the reviewed work sets the stage for a new understanding of RBC-derived relaxing activity in auto-regulation of blood flow and O 2 delivery and of RBC dysfunction in disorders characterized by tissue O 2 deficits, such as sickle cell disease, sepsis, diabetes, and heart failure.
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“Nitrite administered before or during cardiac ischemia has been shown to protect cardiac function and attenuate infarct size in a number of small and large animal models (226, 374, 864).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [864]
In the citing paper
“Notably, other nitrogen-centered molecules, such as nitrite, have been shown to promote S-nitrosation of complex I and attenuate ischemia/reperfusion injury (864).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [864]
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Metadata
- Authors
- Singel, D. J., & Stamler, J. S.
- Affiliations
- Montana State University (US)
- Howard Hughes Medical Institute (US)
- ORCID
- Stamler, Jonathan S.
- Venue
- Annual Review of Physiology
- Publisher
- Annual Reviews
- Published
- 2005-03-17
- Volume
- 67
- Issue
- 1
- Pages
- 99-145
- ISSN
- 0066-4278 (ISSN-L)
- 1545-1585
- OpenAlex
- W1828441724
- Cited by
- 481
- References
- 146
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 16 · 2023: 13 · 2022: 22 · 2021: 16 · 2020: 10 · 2019: 18 · 2018: 15 · 2017: 18 · 2016: 13 · 2015: 20 · 2014: 23 · 2013: 28 · 2012: 30
- FWCI
- 2.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (P01HL042444, 5P01-HL42444)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Hematology › Blood properties and coagulation
- Keywords
- erythrocytes, nitric oxide, hemoglobin, oxygen sensing, vasodilation, vasoconstriction, microcirculation, S-nitrosohemoglobin, blood flow regulation, oxygen delivery, autoregulation, sickle cell disease, sepsis, diabetes mellitus, heart failure
- MeSH terms
- Blood Circulation, Erythrocytes, Hemoglobins, Humans, Microcirculation, Nitric Oxide
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