Submitted on March 11, 2008
Revised on July 24, 2008
Accepted on August 20, 2008
Additive Effect of Red Blood Cell Rigidity and Adherence to Endothelial Cells in Inducing Vascular Resistance
Dhananjay K Kaul1, Alexander Koshkaryev2, Gerhard Artmann3, Gregory Barshtein4*, and Saul Yedgar5
1 Albert Einstein College of Medicine
2 Hebrew University, The Faculty of Medicine
3 FH Aachen Julich
4 The Hebrew University - Hadassah Medical School
5 Hebrew University-Hadassah Medical School
* To whom correspondence should be addressed. E-mail: gregb{at}cc.huji.ac.il.
To explore the contribution of Red Blood Cell (RBC) deformability and interaction with endothelial cells (EC) to circulatory disorders, these RBC properties were modified by treatment with hydrogen peroxide (H2O2), and their effects on vascular resistance were monitored following their infusion into rat mesocecum vasculature. Treatment with 0.5 mM H2O2 increased RBC/EC adherence without significant alteration of RBC deformability. At 5.0 mM H2O2, RBC deformability was considerably reduced, inducing a 3-fold increase in the number of undeformable cells, whereas RBC/EC adherence was not further affected by the increased H2O2 concentration. This enabled the selective manipulation of RBC adherence and deformability, and testing their differential effect on vascular resistance. Perfusion of RBC with enhanced adherence and unchanged deformability (treatment with 0.5 mM H2O2) increased vascular resistance by about 35% as compared with untreated control RBC. Perfusion of 5.0 mM H2O2-treated RBC, with reduced deformability (without additional increase of adherence) further increased vascular resistance by about 60% compared with untreated control RBC. These results demonstrate specific effects of elevated adherence and reduced deformability of oxidized RBC 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 RBC 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.
