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Am J Physiol Heart Circ Physiol 274: H2062-H2073, 1998;
0363-6135/98 $5.00
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Vol. 274, Issue 6, H2062-H2073, June 1998

Test of a two-pathway model for small-solute exchange across the capillary wall

B. M. Fu, R. H. Adamson, and F. E. Curry

Dept. of Human Physiology, School of Medicine, University of California at Davis, Davis, California 95616

We previously proposed a two-pathway model for solute and water transport across vascular endothelium (Fu, B. M., R. Tsay, F. E. Curry, and S. Weinbaum. J. Biomech. Eng. 116: 502-513, 1994) that hypothesized the existence of a continuous slit 2 nm wide along tight junction strands within the interendothelial cleft in parallel with 20 × 150-nm breaks in tight junctions. We tested this model by measuring capillary permeability coefficients (P) to a small solute (sodium fluorescein, radius 0.45 nm), assumed to permeate primarily the 2-nm small pore, and an intermediate-sized solute (FITC-alpha -lactalbumin, radius 2.01 nm) excluded from the small pore. Mean values of the paired diffusive permeability coefficients, Psodium fluorescein and PFITC-alpha -lactalbumin, were 34.4 and 2.9 × 10-6 cm/s, respectively, after corrections for solvent drag and free dye (n = 26). These permeabilities were accounted for by transport through the large-break pathway without the additional capacity of the hypothetical 2-nm pathway. As a further test we examined the relative reductions of Psodium fluorescein and PFITC-alpha -lactalbumin produced by elevated intracellular cAMP. Within 20 min after the introduction of rolipram and forskolin, Psodium fluorescein and PFITC-alpha -lactalbumin decreased to 0.67 and 0.64 times their respective baseline values. These similar responses to permeability decrease were evidence that the two solutes were carried by a common pathway. Combined results in both control and reduced permeability states did not support the hypothesis that a separate pathway across tight junctions is available for solutes with a radius as large as 0.75 nm. If such a pathway is present, then its size must be smaller than that of sodium fluorescein.

quantitative fluorescence microscope photometry; paired measurements on single capillaries; three-dimensional junction-pore matrix model for interendothelial cleft; rolipram; forskolin


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