The DOI matches its Crossref record; 63 of the 63 references it cites were found in a registry or an index.
Transduction of NO-bioactivity by the red blood cell in sepsis: novel mechanisms of vasodilation during acute inflammatory disease
Abstract
Sepsis is an acute inflammatory disease characterized by dysfunctional blood flow and hypotension. Nitric oxide (NO) is elevated during sepsis and plays an integral role in the associated vascular pathology. However, precise mechanisms and functions of NO in sepsis remain unclear. In this study, we show that red blood cells (RBCs) are foci for nitrosative reactions during acute inflammation, resulting in the formation of cells that can promote systemic vascular relaxation in an uncontrolled manner. Specifically, using experimental models of endotoxemia and surgical sepsis, NO adducts were found in the RBCs, including S-nitrosohemoglobin (SNOHb). These RBCs, referred to as septic RBCs, spontaneously stimulated vasodilation in a manner consistent with elevated SNOHb concentrations. Moreover, relaxation was cyclic guanosine monophosphate (cGMP) dependent and was inhibited by RBC lysis and glutathione but not by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5 tetramethylimidazoline 1-oxyl 3-oxide (C-PTIO). The potential mechanism of septic RBC-mediated vasorelaxation is discussed and may involve the intermediate, nitroxyl (HNO). Coupled with data showing that NO adducts in septic RBCs were dependent on the inducible nitric oxide synthase and correlated with plasma nitrite, these findings provide a novel framework to understand mechanisms underlying dysfunctional blood flow responses during sepsis. Specifically, the concept that RBCs directly mediate systemic hypotension through NO-dependent mechanisms is discussed.
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In the citing paper
“exogenous administration of nitrite correlates with increased levels of S-nitrosothiols in red blood cells and other tissues both in vivo and in vitro [25, 43, 46-53].”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [48]
In the citing paper
“Many reports show that nitrite supplementation to intact organisms is associated with a widespread increase in the concentration of this anion and production of NO-derived species such as S-nitrosothiols or nitrosylhemes in several tissues[25, 43, 46, 48, 49, 96].”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [48]
Citations
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Self-citationS-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control
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Essential Roles of S-Nitrosothiols in Vascular Homeostasis and Endotoxic Shock
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Cited by
Sorted by citations
The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics
Lundberg, J. O., Weitzberg, E., & Gladwin, M. T. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2466 · Cited by 2,739
Evolution of adverse changes in stored RBCs
Bennett‐Guerrero, E., Veldman, T. H., Doctor, A., Telen, M. J., Ortel, T. L., Reid, T. S., Mulherin, M. A., Zhu, H., Buck, R. D., Califf, R. M., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708160104 · Cited by 614
Nitrite is a signaling molecule and regulator of gene expression in mammalian tissues
Bryan, N. S., Fernandez, B. O., Bauer, S. M., Garcia-Saura, M. F., Milsom, A. B., Rassaf, T., Maloney, R. E., Bharti, A., Rodriguez, J., & Feelisch, M. (2005) · Nature Chemical Biology · doi:10.1038/nchembio734 · Cited by 518
Hypoxia, red blood cells, and nitrite regulate NO-dependent hypoxic vasodilation
Crawford, J. H. (2006) · Blood · doi:10.1182/blood-2005-07-2668 · Cited by 497
Self-citationSingel, D. J., & Stamler, J. S. (2005) · Annual Review of Physiology · doi:10.1146/annurev.physiol.67.060603.090918 · Cited by 481
Metadata
- Authors
- Crawford, J. H., Chacko, B. K., Pruitt, H. M., Piknova, B., Hogg, N., & Patel, R. P.
- Affiliations
- Medical College of Wisconsin (US)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2004-09-01
- Volume
- 104
- Issue
- 5
- Pages
- 1375-1382
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1987088892
- Cited by
- 111
- References
- 62
- Citations by year
- 2026: 1 · 2025: 1 · 2022: 4 · 2021: 4 · 2020: 1 · 2019: 5 · 2017: 9 · 2016: 3 · 2015: 6 · 2014: 5 · 2013: 6 · 2012: 7
- FWCI
- 5.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL070146, HL 70146)
- National Institute of General Medical Sciences (T32GM008361, T32 GM 08361, GM55792)
- National Institute of Biomedical Imaging and Bioengineering (EB001980, P41EB001980)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Keywords
- sepsis, nitric oxide, erythrocytes, S-nitrosohemoglobin, nitroxyl, vasodilation, endotoxemia, septic shock, hypotension, inducible nitric oxide synthase, plasma nitrite, glutathione, acute inflammation
- MeSH terms
- Acute Disease, Animals, Cecum, Disease Models, Animal, Erythrocytes, Hemoglobins, Ligation, Lipopolysaccharides, Male, Nitric Oxide, Nitrites, Oxygen, Vasodilation, Wounds, Stab, Rats, Sprague-Dawley, Sepsis, Nitric Oxide Synthase, Rats, Nitric Oxide Synthase Type II
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