PLATELET-ACTIVATING-FACTOR MEDIATES ANGIOTENSIN-II-INDUCED PROTEINURIA IN ISOLATED-PERFUSED RAT-KIDNEY

Isolated kidney preparations (IPK) from male Sprague Dawley rats perfu sed at constant pressure were used to evaluate the effect of angiotens in II (AII) and platelet-activating factor (PAF) on renal function and urinary protein excretion. Compared with basal, intrarenal infusion o f AII at 8 ng/min caused a progressive increase in protein excretion ( 11 +/- 6 versus 73 +/- 21 mu g/min) in parallel with a decline in rena l perfusate flow (RPF) (29 +/- 3 versus 18 +/- 3 ml/min). Addition to the perfusate of PAF at 50 nM final concentration also induced protein uria (9 +/- 4 versus 55 +/- 14 mu g/min) but did not change RPF (29 +/ - 3 versus 30 +/- 3 ml/min). Preexposure of isolated kidneys to the PA F receptor antagonist WEB 2086 prevented the increase in urinary prote in excretion induced by AII infusion (basal: 13 +/- 6; post-AII: 12 +/ - 7 mu g/min) but failed to prevent the vasoactive effect of AII (RPF, basal: 30 +/- 2; post-AII: 21 +/- 3 ml/min). In additional experiment s, dexamethasone reduced the proteinuric effect of PAF remarkably. The se results indicate that in isolated kidney preparation: (I) AII infus ion induced proteinuria and decreased RPF; and (2) the effect of AII i n enhancing urinary protein excretion was completely prevented by a sp ecific PAF receptor antagonist, which, however, did not influence the AII-induced fall in RPF. It is suggested that PAF plays a major role i n AII-induced changes in the permselective function of the glomerular capillary barrier.