Cited by 481Hemoglobin structure and functionNitric Oxide and Endothelin EffectsBlood properties and coagulation

CHEMICAL PHYSIOLOGY OF BLOOD FLOW REGULATION BY RED BLOOD CELLS: The Role of Nitric Oxide and S-Nitrosohemoglobin

Singel, David J., Stamler, Jonathan S.·2005·Annual Review of Physiology

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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Registry

Crossref · 10.1146/annurev.physiol.67.060603.090918

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145 of 145 references verified0 citation errors · 0 not checkable

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  • Nitrite administered before or during cardiac ischemia protects cardiac function and attenuates infarct size in small and large animal models.

    “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).”
  • Other nitrogen-centered molecules, such as nitrite, promote S-nitrosation of complex I and attenuate ischemia/reperfusion injury.

    “Notably, other nitrogen-centered molecules, such as nitrite, have been shown to promote S-nitrosation of complex I and attenuate ischemia/reperfusion injury (864).”

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Authors
Singel, D. J., & Stamler, J. S.
Affiliations
  • Montana State University (US)
  • Howard Hughes Medical Institute (US)
Venue
Annual Review of Physiology
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 › Cell Biology › Hemoglobin structure and function
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › 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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