Platelet-activating factor mediates angiotensin II-induced proteinuria in isolated perfused rat kidney.

Abstract

Isolated kidney preparations (IPK) from male Sprague Dawley rats perfused at constant pressure were used to evaluate the effect of angiotensin II (AII) and platelet-activating factor (PAF) on renal function and urinary protein excretion. Compared with basal, intrarenal infusion of AII at 8 ng/min caused a progressive increase in protein excretion (11 +/- 6 versus 73 +/- 21 micrograms/min) in parallel with a decline in renal perfusate flow (RPF) (29 +/- 3 versus 18 +/- 3 ml/min). Addition to the perfusate of PAF at 50 nM final concentration also induced proteinuria (9 +/- 4 versus 55 +/- 14 micrograms/min) but did not change RPF (29 +/- 3 versus 30 +/- 3 ml/min). Preexposure of isolated kidneys to the PAF receptor antagonist WEB 2086 prevented the increase in urinary protein excretion induced by AII infusion (basal: 13 +/- 6; post-AII: 12 +/- 7 micrograms/min) but failed to prevent the vasoactive effect of AII (RPF, basal: 30 +/- 2; post-AII: 21 +/- 3 ml/min). In additional experiments, dexamethasone reduced the proteinuric effect of PAF remarkably. These results indicate that in isolated kidney preparation: (1) AII infusion induced proteinuria and decreased RPF; and (2) the effect of AII in enhancing urinary protein excretion was completely prevented by a specific PAF receptor antagonist, which, however, did not influence the AII-induced fall in RPF. It is suggested that PAF plays a major role in AII-induced changes in the permselective function of the glomerular capillary barrier.

Comparative compositional and functional venomic profiles among venom specimens from juvenile, subadult and adult Russell’s viper ( Daboia siamensis ): correlation with renal pathophysiology in experimental rabbits

“…The underlying mechanism of the alterations in renal hemodynamics in the liberation of PAF from kidney cells by D. siamensis venom may exert a receptor-mediated effect on the afferent arterioles unrelated to other vasoconstrictor mediators, either the RAS [91] or the sympathetic nervous system [92], which can interact with the formation of PAF. The interaction of PAF with these systems would not be likely, since the kidney is a major site of arachidonic acid release and its subsequent enzymatic conversion to multiple bioactive prostanoids via the cyclooxygenase metabolic pathway.…”