In view of its role as a proinflammatory mediator in glomerular injury, we investigated the renal cortical microcirculatory responses to the intrarenal arterial administration of platelet-activating factor (PAF) in the anesthetized euvolemic Munich-Wistar rat. Close arterial administration of PAF led to dose-dependent reductions in renal plasma flow rate (RPF), glomerular filtration rate (GFR), and filtration fraction (FF), in the absence of hypotension or hemoconcentration. Single-nephron (SN) plasma flow rate (Q(A)), SNGFR and SNFF also fell [126 ± 7 to 101 ± 6 nl/min (P <0.005), 40.6 ± 2.1 to 21.5 ± 2.5 nl/min (P <0.005), and 0.33 ± 0.03 to 0.21 ± 0.03 (P <0.025)]. PAF increased pre- and postglomerular arteriolar resistances [2.32 ± 0.14 to 2.73 ± 0.19 (P <0.005) and 1.32 ± 0.13 to 1.45 ± 0.10 1010 dyn · s · cm-5 (P<0.05)]. PAF infusion also led to a dramatic reduction in the mean value for the glomerular capillary ultrafiltration coefficient, K(f) [0.058 ± 0.012 to 0.020 ± 0.003 nl · s-1 · mmHg (P <0.025)]. PAF-induced changes in renal hemodynamics were abolished in the presence of the cyclooxygenase inhibitors, indomethacin and ibuprofen. When administered concomitantly with a thromboxane A2 (TxA2) receptor antagonist, PAF led to significant increases in RPF and GFR. In isolated glomeruli, PAF stimulated the biosynthesis of TxB2 in a dose-dependent manner. Thus PAF depresses rat glomerular function by inducing contraction of arteriolar and mesangial smooth muscle. These effects are likely mediated via the secondary release of TxA2.
|Original language||English (US)|
|Journal||American Journal of Physiology - Renal Fluid and Electrolyte Physiology|
|State||Published - 1989|
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