title: Role of platelet-activating factor in renal function in normal rats and rats with bilateral ureteral obstruction.
abstract: Platelet-activating factor (PAF) is a powerful vasodilator with important effects on kidney function. It has been suggested that the renal effects of PAF are mediated by thromboxane A2 (TxA2). We examined the effect of PAF on renal function in sham-operated rats and rats that had undergone unilateral release of bilateral ureteral obstruction (BUO) of 24-hr duration, a condition in which the synthesis of TxA2 is increased. To eliminate systemic hemodynamic changes, PAF was infused directly into the left renal artery using the lowest dose that affected renal function (2.3 x 10(-13) moles/min). Infusion of PAF significantly decreased the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in normal rats and rats with BUO. Normal (sham-operated) rats pretreated with an inhibitor of TxA2 synthesis also had a significant decrease in GFR after administration of PAF (ERPF also decreased, but not significantly). Rats with BUO pretreated with an inhibitor of TxA2 synthesis had significantly greater basal GFR and ERPF (increases of 72 and 171%, respectively) than untreated BUO rats. Administration of PAF to the former group further increased GFR and ERPF (by 37 and 39%, respectively; P less than 0.001). The role of endogenous PAF was evaluated by administering a specific PAF receptor antagonist. Sham-operated rats pretreated with high doses of the PAF receptor antagonist had significantly higher mean arterial pressure values than normal untreated rats, and had no decrease in GFR and ERPF during PAF infusion. Rats with BUO pretreated with the PAF antagonist had a significant, dose-dependent decrease in basal GFR and ERPF. These data suggest that endogenous PAF has a vasodilatory role in obstructive nephropathy. No significant differences in eicosanoid excretion in the urine corrected per GFR were observed during infusion of PAF in any of the groups examined. In BUO rats with intact TxA2 synthesis, exogenous administration of PAF decreased renal function, presumably through further increases in the production of TxA2. However, when TxA2 production was inhibited, PAF administration increased GFR and ERPF, presumably due to its unopposed vasodilatory properties. The data suggest an important role of PAF in the hemodynamic changes seen in obstructive nephropathy.
authors.affiliation: Renal Division, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: A A
authors.initials: AA
authors.lastname: Reyes
authors.forename: S
authors.initials: S
authors.lastname: Klahr
mesh_terms: D000818:Animals; D005260:Female; D005663:Furans / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects*; D008689:Methacrylates / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects; D013928:Thromboxane A2 / Q000502:physiology / Q000652:urine; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014517:Ureteral Obstruction / Q000188:drug therapy*
chemical_list: D005663:Furans; D008689:Methacrylates; D010972:Platelet Activating Factor; C054893:L 659989; D013928:Thromboxane A2; D013930:Thromboxane-A Synthase; C034364:ozagrel