Graded modulation of frog microvessel permeability to albumin using ionophore A23187

We investigated the exchange of water and macromolecules across venular microvessels after permeability was increased. Quantitative fluorescence microscopy was used to measure albumin permeability coefficients in individually perfused microvessels of decerebrate frogs. Control permeability coefficient was 2.3 ± 0.25 x 10-^-7 cm/s. Solvent drag increased the apparent solute permeability coefficient (Ps)) by 0.57 ± 0.05 x 10^-7 cm/s for each cmH₂O increase in microvessel pressure. The divalent cation ionophore A23187 (0.1-5 μM) produced a transient increase in P(s) to a peak value (within 1-3 min), followed (after 4-8 min) by a sustained increase in permeability (16-43% of peak values). Peak values of P(s) were 13 and 80 times control for 0.1 and 5 μM A23187, respectively. Both diffusion and solvent drag contributed to the sustained increase in P(s). The equivalent pore radius of the structures determining diffusion and solvent drag was ≤25 nm during the sustained increase in permeability, smaller than observed gaps between adjacent endothelial cells. The basement membrane and a fibrous matrix secreted by endothelial cells into the gaps may offer resistance to exchange in the high permeability state.