Platelet-activating factor alters glomerular barrier size selectivity for macromolecules in rats

The effect of platelet-activating factor (PAF) on glomerular permeability to macromolecules was investigated in the isolated kidneys from normal male Sprague-Dawley rats perfused at constant pressure. Compared with basal values, infusion of PAF (10 nM final concentration) into the isolated kidneys induced a progressive and significant increase in protein excretion (6.7 ± 2.7 vs. 40.7 ± 10.4 μg/min, P < 0.01), completely reversible 20 min after PAF infusion was discontinued (8.5 ± 1.3 μg/min). In additional experiments, during PAF infusion the fractional clearance of small neutral dextrans (radius 24-48 Å), defined as the ratio of the clearance of neutral dextrans to the clearance of creatinine, was comparable to preinfusion values, whereas fractional clearance of large dextrans (>50 Å) was significantly elevated (P < 0.005) above preinfusion values. The specific PAF receptor antagonist L 652731 completely prevented the increased fractional clearance of large dextrans induced by PAF. Finally, lowering Ca2+ concentration in the perfusion medium from 2.5 to <0.1 mM markedly reduced proteinuria in isolated kidneys exposed to PAF (80.0 ± 10.3, 42.8 ± 3.1, and 22.0 ± 7.6 μg/min, respectively, for 2.5, 1.25, and <0.1 mM). These results indicate that in isolated perfused kidneys 1) PAF-induced proteinuria is a functional phenomenon reversible on discontinuing PAF infusion, 2) PAF modifies glomerular size-selective properties by increasing transmural passage of large dextran molecules, and 3) PAF-induced change in glomerular permselective properties is dependent on Ca2+ concentration in the extracellular medium.