Transcapillary exchange of 14C-inulin by free diffusion in channels of fused vesicles

Capillary permeability for the extracellular, hydrophilic indicator 14C-inulin, was determined in the autoperfused cat gastrocnemius muscle by bolus injection, venous sampling expts. The capillary diffusion capacity, CDC (the permeability-surface are product, PS), was 0.84 ml/100 g-min, and capillary extraction, E, was 0.307 at a plasma flow of 4.0 ml/100 g-min as average values of 7 expts. Results were compared with 51Cr-EDTA and 57Co-B12 data of previous studies. The findings imply that 14C-inulin is not subject to restricted diffusion across the continuous capillary membranes of skeletal muscle as compared to 51Cr-EDTA as well as 57Co-B12. These hydrophilic indicators pass the capillary barrier at rates proportional to their respective free diffusion coefficients in water. The Pappenheimer equivalent pore radius estimate of 30 A (or slit width of 37 A) and the Karnovsky 40 A interendothelial slit width are inconsistent with the present data which imply a much larger pore size. The transendothelial channel system of fused vesicles is a possible morphological equivalent for the present findings which support the general theory that capillaries of continuous type exhibit similar permeation characteristics regardless of the tissue in which they are located. By kinetic black-box analysis the extravascular distribution volume for 14C-inulin in skeletal muscle was found to be 13.0 ml/100 g. The data indicate that 51Cr-EDTA, which has about the same molecular radius as sucrose, and 14C-inulin have identical extravascular volumes of distribution and that both molecules presumably enter the sarcoplasmic reticulum.