Shedding of the Endothelial Glycocalyx and the Resistance to Flow in Capillaries

Abstract

The endothelial glycocalyx serves as a barrier to transvascular exchange of fluid, macromolecules, and leukocyte‐endothelium (EC) adhesion during the inflammatory process. Shedding of glycosaminoglycans and proteoglycans of the glycocalyx occur in response to several agonists. To elucidate the hemodynamic effects of glycan shedding on capillary resistance to flow during inflammation, intestinal mesentery (rat) was superfused with 10−7 M fMLP. Shedding was quantified by reductions of fluorescently labeled lectin (BS‐1) bound to the EC and reductions in thickness of the barrier to infiltration of 70 kDa dextran (Dx70) on the EC surface. Red cell velocities (two‐slit technique), pressure drops (dual servo‐null method), and capillary hematocrit (direct cell counting) were measured in parallel experiments. Glycocalyx thickness decreased by 80 nm. Capillary resistance rose 18% due to diminished deformability of activated WBCs and fell significantly 26% over a 30 min period, as glycans were shed from the EC surface to increase effective capillary diameter while capillary hematocrit and anatomical diameter remained invariant. This decrease in capillary resistance mitigated the increase in resistance due to diminished WBC deformability and hence these concurrent rheological events may be of equal importance in affecting capillary flow during the inflammatory process.Supported by R01‐HL39286‐20.