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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 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 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 Vogel, J. Articles by Gassmann, M. Search for Related Content PubMed PubMed Citation Articles by Vogel, J. Articles by Gassmann, M. Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 September 2003, Vol. 102, No. 6, pp. 2278-2284 RED CELLS 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-Schönbein, Wolfgang Kuschinsky, and Max Gassmann From the Institute of Veterinary Physiology, Department of Pathology, and Department of Veterinary Pathology, University of Zürich, Switzerland; the Department of Physiology and Pathophysiology and Department of Internal Medicine (Central Laboratories), University of Heidelberg, Germany; the Division of Physiology, Department of Medicine, University of California San Diego, La Jolla; and the Institute of Physiology, Rhenish-Westfalian Technical University of Aachen, Germany. 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 level. 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 values 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 up to 25% of the body weight compared with 8% in wild-type (wt) siblings. Although plasma viscosity did not differ between tg and wt mice, 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 physiologic shear rates. Apart from the nitric oxide–mediated vasodilation we reported earlier, adaptation to high hematocrit levels 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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