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Am J Physiol Renal Physiol 256: F35-F43, 1989;
0363-6127/89 $5.00
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AJP - Renal Physiology, Vol 256, Issue 1 35-F43, Copyright © 1989 by American Physiological Society

ARTICLES

Glomerular responses to platelet-activating factor in the rat: role of thromboxane A2

K. F. Badr, D. K. DeBoer, K. Takahashi, R. C. Harris, A. Fogo and H. R. Jacobson
Division of Nephrology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.

In view of its role as a pro-inflammatory 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 (QA), SNGFR and SNFF also fell [126 +/- 7 to 101 +/- 6 nl/min (P less than 0.005), 40.6 +/- 2.1 to 21.5 +/- 2.5 nl/min (P less than 0.005), and 0.33 +/- 0.03 to 0.21 +/- 0.03 (P less than 0.025)]. PAF increased pre- and postglomerular arteriolar resistances [2.32 +/- 0.14 to 2.73 +/- 0.19 (P less than 0.005) and 1.32 +/- 0.13 to 1.45 +/- 0.10(10)dyn.s.cm-5 (P less than 0.05)]. PAF infusion also led to a dramatic reduction in the mean value for the glomerular capillary ultrafiltration coefficient, Kf [0.058 +/- 0.012 to 0.020 +/- 0.003 nl.s-1.mmHg (P less than 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.


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