Abstract |
Eicosanoid synthesis was studied in a model of in situ glomerulonephritis (gn) in the rat. Unilateral gn was induced by perfusion of left kidneys with 200 micrograms cationized human IgG followed by intravenous (i.v.) autologous anti-human IgG antiserum. Rats developed proteinuria in the first 24 hours and hypercellular gn with leukocyte infiltration in the left kidney. Synthesis of thromboxane B2 (TXB2), prostaglandin E2 ( PGE2) and 6-ketoprostaglandin F 1 alpha(6-keto-PGF 1 alpha) was measured at 6, 12, 18 and 24 hours in isolated glomeruli by radioimmunoassay. In nephritic glomeruli there was a nine-fold rise in TXB2 at six hours (5.35 ng/mg glomerular protein) when compared to control (0.6 ng/mg). TXB2 was still elevated at 24 hours (2.7 +/- 1 ng/mg; control 0.7 +/- 0.2 ng/mg). There were no consistent changes in PGE2 or 6-keto-PGF 1 alpha. No changes were found in right kidneys of nephritic or control rats. Treatment of nephritic rats with a selective thromboxane synthetase inhibitor, dazmegrel (20 mg/kg 8 hourly intraperitoneally), suppressed glomerular TXB2 at 24 hours. TXB2 was also inhibited in right (non-nephritic) kidneys and serum. Dazmegrel did not inhibit proteinuria or glomerular hypercellularity. We conclude there is a major increase in glomerular TXB2 in this model which does not play an essential role in the development of proteinuria or cellular infiltration.
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Authors | H T Cook, V Cattell, J Smith, J A Salmon, S Moncada |
Journal | Clinical nephrology
(Clin Nephrol)
Vol. 26
Issue 4
Pg. 195-202
(Oct 1986)
ISSN: 0301-0430 [Print] Germany |
PMID | 3490944
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Imidazoles
- Prostaglandins E
- dazmegrel
- Thromboxane B2
- 6-Ketoprostaglandin F1 alpha
- Thromboxane-A Synthase
- Dinoprostone
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Topics |
- 6-Ketoprostaglandin F1 alpha
(biosynthesis)
- Animals
- Dinoprostone
- Glomerulonephritis
(drug therapy, etiology, pathology)
- Imidazoles
(therapeutic use)
- Kidney Glomerulus
(metabolism, pathology)
- Prostaglandins E
(biosynthesis)
- Radioimmunoassay
- Rats
- Rats, Inbred Lew
- Thromboxane B2
(biosynthesis)
- Thromboxane-A Synthase
(antagonists & inhibitors)
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