Capillary Permeability to Lipid-Soluble Molecules

Abstract

Various organic nonelectrolytes were added to the blood perfusing the isolated hindlimb of the cat, and the osmotic effects produced thereby were measured. These effects are greater and persist longer for those substances which penetrate the capillary walls more slowly. On the basis of their olive-oil: water partition coeffs., the test substances were classified lipid-soluble (partition coeff. >0.01) or lipid-insoluble (p.c< 0.001). The lipid-soluble molecules, i.e., urethane, paraldehyde, antipyrine, diacetin and triacetin, penetrate the capillary wall much more rapidly than the lipid-insoluble molecules of comparable sizes, i.e., urea, ethylene glycol, glycerol and glucose. The rates of penetration are directly related to the oil: water partition coeffs., both for a series of glycerol derivatives and for the single substance antipyrine, the lipid-solubility of which is markedly decreased at low temps. Lipid-insoluble compounds and water are believed to pass through the capillary wall in water-filled pores of molecular dimensions, making up only a small fraction of the total endothelial surface area. In order to account for the more rapid diffusion of lipid-soluble molecules, the hypothesis has been made that these may penetrate the relatively large urea afforded by the endothelial cell membranes, in accordance with the high permeability of cell membranes in general to lipid-soluble molecules.