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Blood, 15 July 2005, Vol. 106, No. 2, pp. 734-739. Prepublished online as a Blood First Edition Paper on March 17, 2005; DOI 10.1182/blood-2005-02-0567. This Article Full Text (PDF) All Versions of this Article: 2005-02-0567v1 106/2/734    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dejam, A. Articles by Schechter, A. N Search for Related Content PubMed PubMed Citation Articles by Dejam, A. Articles by Schechter, A. N Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 10, 2005 Accepted March 13, 2005 Erythrocytes are the major intravascular storage sites of nitrite in human blood Andre Dejam, Christian J Hunter, Mildred M Pelletier, Lewis L Hsu, Roberto F Machado, Shruti Shiva, Gordon G Power, Malte Kelm, Mark T Gladwin, and Alan N Schechter* Molecular Medicine Branch, NIDDK, NIH, Bethesda, MD, USA Vascular Therapeutics Section, Cardiovascular Branch, NHLBI, NIH, Bethesda, MD, USA; Center for Perinatal Biology, School of Medicine, Loma Linda University, Loma Linda, CA, USA Molecular Medicine Branch, NIDDK, NIH, Bethesda, MD, USA; Vascular Therapeutics Section, Cardiovascular Branch, NHLBI, NIH, Bethesda, MD, USA Vascular Therapeutics Section, Cardiovascular Branch, NHLBI, NIH, Bethesda, MD, USA Center for Perinatal Biology, School of Medicine, Loma Linda University, Loma Linda, CA, USA Department of Medicine, Division of Cardiology, Pulmonary Diseases, Angiology, Heinrich-Heine University, Duesseldorf, Germany Vascular Therapeutics Section, Cardiovascular Branch, NHLBI, NIH, Bethesda, MD, USA; Critical Care Medicine Department, Clinical Center, Bethesda, MD, USA * Corresponding author; email: aschecht{at}helix.nih.gov. Plasma levels of nitrite ions have been used as an index of nitric oxide synthase (NOS) activity in vivo. Recent data suggest that nitrite is a potential intravascular repository for nitric oxide (NO), bioactivated by a nitrite reductase activity of deoxyhemoglobin. The precise levels and compartmentalization of nitrite within blood and erythrocytes have not been determined. Nitrite levels in whole blood and erythrocytes were determined using reductive chemiluminescence in conjunction with a ferricyanide-based hemoglobin oxidation assay to prevent nitrite destruction. This method yields sensitive and linear measurements of whole blood nitrite over 24 h at room temperature. Nitrite levels measured in plasma, erythrocytes, and whole blood from 15 normal volunteers were 121 ± 9, 288 ± 47, and 176 ± 17 nmol/L, indicating a surprisingly high concentration of nitrite within erythrocytes. The majority of nitrite in erythrocytes is located in the cytosol unbound to proteins. In humans, we found a significant artery-to-vein gradient of nitrite in whole blood and erythrocytes. Shear-stress and acetylcholine-mediated stimulation of endothelial NOS significantly increased venous nitrite levels. These studies suggest a dynamic intravascular NO metabolism in which eNOS-derived NO is stabilized as nitrite, transported by erythrocytes and consumed during arterial-to-venous transit. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Nitrite "defixation" H. Franklin Bunn Blood 2005 106: 390-391. [Full Text] [PDF] This article has been cited by other articles: H. G. Bohlen, X. Zhou, J. L. Unthank, S. J. Miller, and R. Bills Transfer of nitric oxide by blood from upstream to downstream resistance vessels causes microvascular dilation Am J Physiol Heart Circ Physiol, October 1, 2009; 297(4): H1337 - H1346. [Abstract] [Full Text] [PDF] C. Dezfulian, S. Shiva, A. Alekseyenko, A. Pendyal, D.G. Beiser, J. 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