The DOI matches its Crossref record; 145 of the 146 references it cites were found in a registry or an index.
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Citations
Cites
Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor
Palmer, R. M. J., Ferrige, A. G., & Moncada, S. (1987) · Nature · doi:10.1038/327524a0 · Cited by 10,704
A Multicenter, Randomized, Controlled Clinical Trial of Transfusion Requirements in Critical Care
Hébert, P. C., Wells, G., Blajchman, M. A., Marshall, J., Martin, C., Pagliarello, G., Tweeddale, M., Schweitzer, I., & Yetisir, E. (1999) · New England Journal of Medicine · doi:10.1056/nejm199902113400601 · Cited by 5,187
Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide.
Ignarro, L. J., Buga, G. M., Wood, K. S., Byrns, R. E., & Chaudhuri, G. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.24.9265 · Cited by 5,074
Perutz, M. F. (1970) · Nature · doi:10.1038/228726a0 · Cited by 2,914
Biochemistry of nitric oxide and its redox-activated forms
Stamler, J. S., Singel, D. J., & Loscalzo, J. (1992) · Science · doi:10.1126/science.1281928 · Cited by 2,744
Self-citationBesarab, A., Bolton, W. K., Browne, J. K., Egrie, J. C., Nissenson, A. R., Okamoto, D. M., Schwab, S. J., & Goodkin, D. A. (1998) · New England Journal of Medicine · doi:10.1056/nejm199808273390903 · Cited by 1,930
Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation
Cosby, K., Partovi, K. S., Crawford, J. H., Patel, R. P., Reiter, C. D., Martyr, S., Yang, B. K., Waclawiw, M. A., Zalos, G., Xu, X., et al. (2003) · Nature Medicine · doi:10.1038/nm954 · Cited by 1,807
Anemia and Blood Transfusion in Critically Ill Patients
Vincent, J. (2002) · JAMA · doi:10.1001/jama.288.12.1499 · Cited by 1,794
Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle
Bolotina, V. M., Najibi, S., Palacino, J. J., Pagano, P. J., & Cohen, R. A. (1994) · Nature · doi:10.1038/368850a0 · Cited by 1,690
S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control
Jia, L., Bonaventura, C., Bonaventura, J., & Stamler, J. S. (1996) · Nature · doi:10.1038/380221a0 · Cited by 1,592
Self-citation
Research works printed but not linked: 14
- Bates JN, 1991, Basic Res. Cardiol., 86, 17
- Gaston B, 1994, J. Pharmacol. Exp. Ther., 268, 978
- Stamler JS, 1995, Curr. Top. Microbiol. Immunol., 196, 19
- Sellke FW, 1990, Am. J. Physiol., 258, H515
- Jackson WF, 1987, Am. J. Physiol., 253, H1120
- Guyton AC, 1964, Circ. Res., 15, 60
- Roach RC, 1999, Am. J. Physiol., 276, H438
- Deleted in press
- Coburn R, 1967, Fed. Proc., 26, 334 (Abstr.)
- Kruszyna R, 1987, J. Pharmacol. Exp. Ther., 241, 307
- Reutov VP, 1998, Biochemistry (Mosc), 63, 874
- 10.1021/ja036693b · DOI · Paper page
- Chen B, 1999, Tsin. Sci. Tech., 4, 3024
- Foster MW, 2004, Hypertension
Cited by
Sorted by citations
Protein S-nitrosylation: Purview and parameters
Hess, D. T., Matsumoto, A., Kim, S.-O., Marshall, H. E., & Stamler, J. S. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1569 · Cited by 2,153
Self-citationReactive oxygen species generating systems meeting challenges of photodynamic cancer therapy
Zhou, Z., Song, J., Nie, L., & Chen, X. S. (2016) · Chemical Society Reviews · doi:10.1039/c6cs00271d · Cited by 2,121
Cysteine-Mediated Redox Signaling: Chemistry, Biology, and Tools for Discovery
Paulsen, C. E., & Carroll, K. S. (2013) · Chemical Reviews · doi:10.1021/cr300163e · Cited by 1,313
Methods to detect nitric oxide and its metabolites in biological samples
Bryan, N. S., & Grisham, M. B. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.04.026 · Cited by 1,005
Regulation of coronary blood flow during exercise
Duncker, D. J., & Bache, R. J. (2008) · Physiological Reviews · doi:10.1152/physrev.00045.2006 · Cited by 936
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
