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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 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 Citation Map 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 Hemostasis, Thrombosis, and Vascular Biology Red Cells Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Erythrocytes are the major intravascular storage sites of nitrite in human blood André Dejam, Christian J. Hunter, Mildred M. Pelletier, Lewis L. Hsu, Roberto F. Machado, Sruti Shiva, Gordon G. Power, Malte Kelm, Mark T. Gladwin, and Alan N. Schechter From the Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Disease (NIDDK); National Institutes of Health (NIH), Bethesda, MD; Vascular Therapeutics Section, Cardiovascular Branch, National Heart, Lung and Blood Institute, NIH, Bethesda, MD; St Christopher's Hospital for Children, Drexel University, Philadelphia, PA; Center for Perinatal Biology, School of Medicine, Loma Linda University, Loma Linda, CA; Department of Medicine, Division of Cardiology, Pulmonary Diseases, Angiology, Heinrich-Heine University, Düsseldorf, Germany; Critical Care Medicine Department, Clinical Center, Bethesda, MD. 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 hours at room temperature. Nitrite levels measured in plasma, erythrocytes, and whole blood from 15 healthy volunteers were 121 plus or minus 9, 288 plus or minus 47, and 176 plus or minus 17 nM, 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 endothelial NOS-derived NO is stabilized as nitrite, transported by erythrocytes, and consumed during arterial-to-venous transit. (Blood. 2005;106:734-739) 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: V. C. Sandrim, A. C.T. Palei, I. F. Metzger, V. A. Gomes, R. C. Cavalli, and J. E. Tanus-Santos Nitric Oxide Formation Is Inversely Related to Serum Levels of Antiangiogenic Factors Soluble Fms-Like Tyrosine Kinase-1 and Soluble Endogline in Preeclampsia Hypertension, August 1, 2008; 52(2): 402 - 407. [Abstract] [Full Text] [PDF] F. M. Gonzalez, S. Shiva, P. S. Vincent, L. A. Ringwood, L.-Y. Hsu, Y. Y. Hon, A. H. Aletras, R. O. Cannon III, M. T. Gladwin, and A. E. 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[Abstract] [Full Text] [PDF] G. G. Power, S. L. Bragg, B. T. Oshiro, A. Dejam, C. J. Hunter, and A. B. Blood A novel method of measuring reduction of nitrite-induced methemoglobin applied to fetal and adult blood of humans and sheep J Appl Physiol, October 1, 2007; 103(4): 1359 - 1365. [Abstract] [Full Text] [PDF] T. Rassaf, T. Lauer, C. Heiss, J. Balzer, S. Mangold, T. Leyendecker, J. Rottler, C. Drexhage, C. Meyer, and M. Kelm Nitric oxide synthase-derived plasma nitrite predicts exercise capacity Br. J. Sports Med., October 1, 2007; 41(10): 669 - 673. [Abstract] [Full Text] [PDF] S. Shiva, M. N. Sack, J. J. Greer, M. Duranski, L. A. Ringwood, L. Burwell, X. Wang, P. H. MacArthur, A. Shoja, N. Raghavachari, et al. Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transfer J. Exp. Med., September 3, 2007; 204(9): 2089 - 2102. [Abstract] [Full Text] [PDF] M. P. Coggins and K. D. 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