Glomerular responses to platelet-activating factor in the rat: role of thromboxane A2.
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.
Badr
K F
KF
Division of Nephrology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
DeBoer
D K
DK
Takahashi
K
K
Harris
R C
RC
Fogo
A
A
Jacobson
H R
HR
D000818:Animals; D001794:Blood Pressure; D015232:Dinoprostone / Q000378:metabolism; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007678:Kidney Glomerulus / Q000187:drug effects*; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D013928:Thromboxane A2 / Q000378:metabolism*; D014462:Ultrafiltration
D010972:Platelet Activating Factor; D013928:Thromboxane A2; D015232:Dinoprostone