Additive effect of red blood cell rigidity and adherence to endothelial cells in inducing vascular resistance

• Published in: American journal of physiology. Heart and circulatory physiology 2008-10, Vol.295 (4), p.H1788-H1793
• Main Authors: Kaul, D. K, Koshkaryev, A, Artmann, G, Barshtein, G, Yedgar, S
• Format: Article
• Language: English
• Subjects: Cell Adhesion - drug effects; Cell Line, Transformed; Cells; Dose-Response Relationship, Drug; Effects; Endothelial Cells - metabolism; Erythrocyte Deformability - drug effects; Erythrocytes; Erythrocytes - drug effects; Erythrocytes - metabolism; Hemorheology; Humans; Hydrogen Peroxide - pharmacology; Oxidants - pharmacology; Oxidation; Rodents; Studies; Vascular Resistance - drug effects
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.253.2008

1 Hematology Division, Albert Einstein College of Medicine, Bronx, New York; 2 Department of Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem, Israel; and 3 Institute of Bioengineering, Department Cell Biophysics, Aachen University of Applied Sciences, Juelich, Germany Submitted 11 March 2008 ; accepted in final form 20 August 2008 To explore the contribution of red blood cell (RBC) deformability and interaction with endothelial cells (ECs) to circulatory disorders, these RBC properties were modified by treatment with hydrogen peroxide (H 2 O 2 ), and their effects on vascular resistance were monitored following their infusion into rat mesocecum vasculature. Treatment with 0.5 mM H 2 O 2 increased RBC/EC adherence without significant alteration of RBC deformability. At 5.0 mM H 2 O 2 , RBC deformability was considerably reduced, inducing a threefold increase in the number of undeformable cells, whereas RBC/EC adherence was not further affected by the increased H 2 O 2 concentration. This enabled the selective manipulation of RBC adherence and deformability and the testing of their differential effect on vascular resistance. Perfusion of RBCs with enhanced adherence and unchanged deformability (treatment with 0.5 mM H 2 O 2 ) increased vascular resistance by about 35% compared with untreated control RBCs. Perfusion of 5.0 mM H 2 O 2 -treated RBCs, with reduced deformability (without additional increase of adherence), further increased vascular resistance by about 60% compared with untreated control RBCs. These results demonstrate the specific effects of elevated adherence and reduced deformability of oxidized RBCs on vascular resistance. These effects can be additive, depending on the oxidation conditions. The oxidation-induced changes applied in this study are moderate compared with those observed in RBCs in pathological states. Yet, they caused a considerable increase in vascular resistance, thus demonstrating the potency of RBC/EC adherence and RBC deformability in determining resistance to blood flow in vivo. erythrocyte rheology; aggregability; adhesion; circulatory disorders Address for reprint requests and other correspondence: G. Barshtein, Dept. of Biochemistry, Hebrew Univ.-Hadassah Medical School, Jerusalem, Israel 91120 (e-mail: gregb{at}cc.huji.ac.il )