DIRECT EFFECTS OF PLATELET-ACTIVATING-FACTOR ON GLOMERULAR CAPILLARY-PERMEABILITY

Platelet-activating factor (PAF) is an important mediator of injury in acute renal failure and glomerulonephritis. Intrarenal infusion of PA F reduces glomerular filtration rate and renal plasma flow and increas es glomerular permselectivity via its renal hemodynamic and/or immunol ogic effects. Direct effects of PAF on glomerular capillary permeabili ty are not known. We studied the direct effects of PAF on mesangial co ntraction (a measure of filtration area), glomerular capillary hydraul ic conductivity (L-p) and capillary albumin permeability (P-albumin) G lomeruli were isolated from Sprague-Dawley rats and incubated with or without various concentrations of PAF (10(-9), 10(-7) and 10(-5) M) fo r up to 5 h at 37 degrees C. Mesangial contraction (percent change in glomerular volume) was assessed from the gradual decrease in volume of glomeruli during 20 min of incubation with PAF. L-p was calculated fr om the rate of change in glomerular volume during the 0.1 s of capilla ry expansion in response to a transcapillary oncotic gradient. P-album in was calculated from a change in relative volume of glomeruli in res ponse to an oncotic gradient. Mesangial contraction was maximal after 20 min of incubation and was concentration dependent (5.2+/-0.9, 7.9+/ -1.0 and 10.0+/-1.0%, respectively, with PAF 10(-9), 10(-7) and 10(-5) M). Incubation of glomeruli with PAF 10(-7) M for 60 min at 37 degree s C caused a significant decrease in L-p (2.25+/-0.30 vs. control 3.12 +/-0.28 mu l . min(-1) . mm Hg-1 . cm(-1), n = 5). P-albumin of glome ruli incubated with PAF was unchanged up to 2 h but increased signific antly with the highest concentration of PAF (10(-5) M) after 2 h of in cubation (0.60+/-0.18, n = 15, vs. control 0.00 +/-0.08, n = 20), wher eas lower concentrations of PAF (10(-7) or 10(-9) M) required at least 5 h of incubation with glomeruli to cause a significant increase in P -albumin (0.45+/-0.09 and 0.48+/-0.07, respectively, n = 15, vs. contr ol 0.00+/-0.08, n = 15). We conclude that PAF has multiple direct effe cts on glomerular functions, which are time dependent and may contribu te to the altered capillary permeability in vivo.