Platelet-activating factor is a potent stimulus for renal prostaglandin synthesis: possible significance in unilateral ureteral obstruction.
Platelet-activating factor (PAF), a lipid with potent platelet-stimulating and hypotensive properties, has been shown to stimulate the release of prostaglandins (PGs) from a number of cell types. It is produced by a variety of inflammatory cells and the renal medulla. However, no studies to date have examined the effect of PAF on the intact kidney. We, therefore, studied the effect of bolus injections of PAF on the isolated perfused rabbit kidney subjected to aseptic ureteral ligation for 72 hr. Intrarenal resistance and release of PGs by both the hydronephrotic (HNK) and contralateral kidney (CLK) were quantified. Intrarenal administration of PAF causes a dose-dependent stimulation of the release of PGE2, thromboxane B2 (TxB2) and the PGI2 metabolite, 6-keto-PGF1 alpha from the HNK and CLK. The magnitude of the release from the HNK is much greater than that for the CLK. A 100-ng bolus injection of PAF into the HNK results in the release of 1561.0 +/- 312.0 and 117.7 +/- 38.2 ng of PGE2 and TxB2, respectively, whereas administration of this dose to the CLK causes 291.0 +/- 35.0 ng of PGE2 and 19.0 +/- 4.2 ng of TxB2 to be released. Renal vascular resistance (RVR) is increased by PAF in the HNK. Product identity was confirmed using selective inhibitors and bioassay. These data show that PAF is a potent stimulus for renal PG release and that this release may have vascular consequences.
D000818:Animals; D001681:Biological Assay; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D013270:Stomach / Q000187:drug effects; D013929:Thromboxane B2 / Q000378:metabolism; D013997:Time Factors; D014517:Ureteral Obstruction / Q000378:metabolism*
D010972:Platelet Activating Factor; D011453:Prostaglandins; D011458:Prostaglandins E; D013929:Thromboxane B2; D015232:Dinoprostone