Effect of thromboxane synthesis inhibition in a model of membranous nephropathy.
The effect of the thromboxane synthesis inhibitor UK 38485 on glomerular filtration rate (GFR) and proteinuria was evaluated in a rat model of unilateral membranous nephropathy. Two and 24 hours following perfusion of kidneys with cationized human IgG and i.v. administration of anti-human IgG-antiserum (in situ ICGN), glomerular thromboxane B2 (TxB2) formation was significantly higher (2 hr: 448 +/- 116 pg/mg protein/min; 24 hr: 173 +/- 21 pg/mg protein/min) compared to control (C) kidneys (2 hr: 173 +/- 21 pg/mg protein/min, P less than 0.005; 24 hr: 154 +/- 17 pg/mg protein/min, P less than 0.025). Two and seven days after induction of ICGN these differences were no longer present. Pretreatment with the thromboxane synthesis inhibitor UK 38485 prevented the decrease in GFR, which occurred two hours after induction of the glomerular disease (without UK: 161 +/- 31; with UK 325 +/- 21 microliters/100 g body wt/min). This UK 38485 effect on GFR was no longer detectable at 24 hours, two days and seven days. Initiation of glomerular immune injury was followed by significant proteinuria which averaged 250 +/- 85 mg/24 hr at day two. UK 38485 treatment, which reduced TxB2 formation in isolated glomeruli by 90% did not influence proteinuria. These data demonstrate that induction of heterologous, in situ immune complex glomerulonephritis stimulates glomerular thromboxane B2 formation, an effect which partially modulates the decrease in GFR at two hours. Thromboxane, however, does not seem to play a role in the mediation of proteinuria in this animal model.
Thaiss
F
F
Department of Medicine, University of Frankfurt, Federal Republic of Germany.
Germann
P J
PJ
Kahf
S
S
Schoeppe
W
W
Helmchen
U
U
Stahl
R A
RA
D000818:Animals; D005919:Glomerular Filtration Rate; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy*; D007093:Imidazoles / Q000627:therapeutic use*; D011507:Proteinuria / Q000188:drug therapy; D051381:Rats; D013928:Thromboxane A2 / Q000502:physiology*; D013929:Thromboxane B2 / Q000502:physiology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D013997:Time Factors
D007093:Imidazoles; C039242:dazmegrel; D013929:Thromboxane B2; D013928:Thromboxane A2; D013930:Thromboxane-A Synthase