title: Test of a two-pathway model for small-solute exchange across the capillary wall.
abstract: 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 x 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 x 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.
authors.affiliation: Dept. of Human Physiology, School of Medicine, University of California at Davis, Davis, California 95616, USA.
authors.forename: B M
authors.initials: BM
authors.lastname: Fu
authors.forename: R H
authors.initials: RH
authors.lastname: Adamson
authors.forename: F E
authors.initials: FE
authors.lastname: Curry
mesh_terms: D000818:Animals; D001834:Body Water / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D003287:Contrast Media; D019793:Fluorescein / Q000493:pharmacokinetics; D016650:Fluorescein-5-isothiocyanate / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D007768:Lactalbumin / Q000493:pharmacokinetics; D008297:Male; D008955:Models, Cardiovascular; D011760:Pyrrolidinones / Q000494:pharmacology; D011894:Rana pipiens; D020889:Rolipram; D019108:Tight Junctions / Q000378:metabolism
chemical_list: D003287:Contrast Media; D005456:Fluorescent Dyes; D011760:Pyrrolidinones; D005576:Colforsin; D007768:Lactalbumin; D016650:Fluorescein-5-isothiocyanate; D020889:Rolipram; D019793:Fluorescein