Elevated capillary tube hematocrit reflects degradation of endothelial cell glycocalyx by oxidized LDL

Proteoglycans and plasma proteins bound to the endothelial cell glycocalyx are essential for vascular function, but at the same time, they lower capil lary tube hematocrit by reducing capillary volume available to flowing bloo d. Because oxidized low-density lipoproteins (oxLDL) reduce the effective t hickness of the glycocalyx (Vink H, Constantinescu AA, and Spaan JAE. Circu lation 101: 1500-1502, 2000), we designed the present study to determine wh ether this is caused by pathological degradation of glycocalyx constituents or increased glycocalyx deformation by elevated shear forces of flowing bl ood. Capillaries from the right cremaster muscle of 24 hamsters were examin ed by using intravital microscopy after systemic administration of normal L DL (n = 4), moderate oxLDL (6-h oxidation with CuSO4, n = 7), severe oxLDL (18-h oxidation, n = 5), and moderate oxLDL plus superoxide dismutase (SOD) and catalase (n = 8). Capillary tube hematocrit increased from 0.16 +/- 0. 03 to 0.37 +/- 0.05 and from 0.15 +/- 0.01 to 0.31 +/- 0.03 after moderate oxLDL and severe oxLDL, respectively. These changes were paralleled by incr eases in red blood cell flux from 8.7 +/- 1.9 to 13.8 +/- 3 and from 10.7 /- 2.1 to 16.3 +/- 3.2 cells/s after moderate oxLDL and severe oxLDL, respe ctively, in the absence of changes in anatomic capillary diameter. Red bloo d cell velocity, as a measure for the shear forces on the glycocalyx, was n ot affected by oxLDL, whereas tissue pretreatment with SOD and catalase com pletely abolished the effects of oxLDL on glycocalyx thickness, capillary h ematocrit, and red blood cell flux. We conclude that elevation of capillary tube hematocrit by oxLDL reflects degradation of the endothelial glycocaly x by oxygen-derived free radicals.