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 PAF reduces glomerular filtration rate and renal plasma flow and increases glomerular permselectivity via its renal hemodynamic and/or immunologic effects. Direct effects of PAF on glomerular capillary permeability are not known. We studied the direct effects of PAF on mesangial contraction (a measure of filtration area), glomerular capillary hydraulic conductivity (L[p]) and capillary albumin permeability (P[albumin]). Glomeruli were isolated from Sprague-Dawley rats and incubated with or without various concentrations of PAF (10[-9], 10[-7] and 10[-5] M) for 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 from the rate of change in glomerular volume during the 0.1 s of capillary expansion in response to a transcapillary oncotic gradient. P(albumin) was calculated from a change in relative volume of glomeruli in response 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 degrees C caused a significant decrease in L(p) (2.25+/-0.30 vs. control 3.12+/-0.28 microl x min(-1) x mm Hg(-1) x cm(-1), n = 5). P(albumin) of glomeruli incubated with PAF was unchanged up to 2 h but increased significantly with the highest concentration of PAF (10(-5) M) after 3 h of incubation (0.60+/-0.18, n=15, vs. control 0.00+/-0.08, n = 20), whereas 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. control 0.00+/-0.08, n=15). We conclude that PAF has multiple direct effects on glomerular functions, which are time dependent and may contribute to the altered capillary permeability in vivo.
Sharma
R
R
Department of Medicine, Froedtert Memorial Lutheran Hospital, Milwaukee, Wisc., USA.
Sharma
M
M
Li
J Z
JZ
McCarthy
E T
ET
Savin
V J
VJ
D000418:Albumins / Q000493:pharmacokinetics; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000418:Albumins; D010972:Platelet Activating Factor