Variable restriction of albumin diffusion across inflamed cerebral microvessels of the anaesthetized rat

1. The possibility of restricted diffusion of macromolecules in single cerebral venular capillaries that have become leaky due to inflammation was investigated by comparing the permeabilities to Lucifer Yellow (457 Da; PLY) and rhodamine-labelled albumin (69 kDa; PRh-A). 2. The dyes were trapped between two micro-occlusion probes and the permeabilities were measured from the rates of decrease in dye fluorescence at low intraluminal hydrostatic pressure. 3. Removal of one probe had little effect on PLY but did reduce PRh-A, consistent with the influence of convection on diffusion through 22 nm wide transendothelial slits 1 micron deep. 4. Direct comparisons were made over time between PLY and PRh-A in six vessels while hydrostatic pressure effects were controlled. In all vessels PRh-A:PLY varied from being similar to the ratio of the free diffusion coefficients to virtually zero even though PLY remained high. The question of the source of this variable restriction to albumin is discussed in terms of the secretion and sloughing of glycosaminoglycans and the possible role of transient formation of transendothelial gaps.