SOLVENT DRAG OF LDL ACROSS MAMMALIAN ENDOTHELIAL BARRIERS WITH INCREASED PERMEABILITY

We investigated the mechanisms of hamster low-density lipoprotein (LDL) transport across the endothelial barrier in individually perfused venular microvessels in hamster mesentery. These experiments are the first to use microperfusion techniques and quantitative fluorescence microscopy to investigate LDL transport across mammalian microvessel endothelium. The apparent permeability coefficient for hamster LDL, P-sLDL, rose from 2.7 x 10(-7) cm/s at control to 23.2 x 10(-7) cm/s at the peak of the biphasic increase in microvessel permeability after exposure of the vessels to 100 mu M histamine. Close to the peak, P-sLDL rose 1.85 x 10(-7) cm/s for every centimeter of H2O increase in hydrostatic pressure. Thus, at a mean pressure of 11.3 cmH(2)O, 90% of the LDL flux was coupled to transendothelial water flow by a solvent drag mechanism. The corresponding solvent drag reflection coefficient for hamster LDL was estimated to be similar to 0.8. These results are consistent with sieving hamster LDL (effective radius 14.9 nm) through equivalent pores of similar to 22 nm radius. Similar results were found with human LDL (effective radius 13.2 nm) in hamster microvessels. The results provide a bridge between studies of LDL transport across cultured endothelial barriers, where high diffusive permeability coefficients to LDL may obscure the contributions of solvent drag, and studies in whole animals, where the consequences of sieving of LDL at the vessel wall, even in the high permeability state, have not received much attention.