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Prepublished online as a Blood First Edition Paper on May 15, 2003; DOI 10.1182/blood-2003-01-0283. This Article Full Text (PDF) All Versions of this Article: 2003-01-0283v1 102/6/2278    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 Vogel, J. Articles by Gassmann, M. Search for Related Content PubMed PubMed Citation Articles by Vogel, J. Articles by Gassmann, M. Social Bookmarking                   What's this? Submitted January 29, 2003 Accepted May 3, 2003 Transgenic mice overexpressing erythropoietin adapt to excessive erythrocytosis by regulating blood viscosity Johannes Vogel, Isabel Kiessling, Katja Heinicke, Thomas Stallmach, Pete Ossent, Olga Vogel, Michael Aulmann, Thomas Frietsch, Holger Schmid-Schoenbein, Wolfgang Kuschinsky, and Max Gassmann* Institute of Veterinary Physiology, University of Zuerich, Zuerich, Switzerland Department of Pathology, University of Zuerich, Zuerich, Switzerland Department of Veterinary Pathology, University of Zuerich, Zuerich, Switzerland Department of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany Division of Physiology, Department of Medicine, University of California at San Diego, La Jolla, CA, USA Institute of Physiology, RWT-University of Aachen, Aachen, Germany * Corresponding author; email: maxg{at}access.unizh.ch. Severe elevation of red blood cell number is often associated with hypertension and thromboembolism resulting in severe cardiovascular complications. However, some individuals such as high altitude dwellers cope well with an increased hematocrit. We analyzed adaptive mechanisms to excessive erythrocytosis in our transgenic (tg) mice that due to hypoxia-independent erythropoietin (Epo) overexpression reached hematocrit values of 0.8 to 0.9 without alteration of blood pressure, heart rate or cardiac output. Extramedullar erythropoiesis occurred in the tg spleen leading to splenomegaly. Upon splenectomy, hematocrit in tg mice decreased from 0.89 to 0.62. Tg mice showed doubled reticulocyte counts and an increased mean corpuscular volume. In tg mice plasma volume was not elevated whereas blood volume was 25% of the body weight compared to 8% in wildtype (wt) siblings. While plasma viscosity did not differ between tg and wt, tg whole-blood viscosity increased to a lower degree (4-fold) than expected from corresponding hemoconcentrated wt blood (8-fold). This moderate increase in viscosity is explicable by the up to 3-fold higher elongation of tg erythrocytes at physiological shear rates. Apart from the nitric oxide mediated vasodilation we reported earlier, adaptation to high hematocrit in tg mice involves regulated elevation of blood viscosity by increasing erythrocyte flexibility. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Mihov, J. Vogel, M. Gassmann, and A. Bogdanova Erythropoietin activates nitric oxide synthase in murine erythrocytes Am J Physiol Cell Physiol, August 1, 2009; 297(2): C378 - C388. [Abstract] [Full Text] [PDF] E. van Rooijen, E. E. Voest, I. Logister, J. Korving, T. Schwerte, S. Schulte-Merker, R. H. Giles, and F. 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