Nephrol Dial Transplant (1989) 4: 625-631
© 1989 European Renal Association-European Dialysis and Transplant Association
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The Inhibition of Thromboxane Synthesis Has No Influence on HgCl2-Induced Acute Renal Failure in the Rat
1Nephrology Department, University Hospital Ghent, Belgium 2Department of Pharmacology, University of Antwerp Belgium
Correspondence and offprint requests to: Correspondence and offprint requests to: R. Vanholder, Nephrology Department, University Hospital, De Pintelaan, 185, B-9000 Ghent, Belgium. Tel. 091 40.45.24
Renal function parameters and urinary thromboxane B2-excretion were studied in the rat in HgCl2-induced acute renal failure. Studies were performed before and 3 h after the inhibition of thromboxane synthesis alone, after HgCl2 alone, or after the combination of HgCl2 and thromboxane-synthesis inhibition. Thromboxane-synthesis inhibition alone by indomethacin (5 mg/kg i.v.), imidazole (25 and 50 µmol/kg per min i.v.) and dazoxiben (5 mg/kg i.v.) had no effect on glomerular filtration rate (GFR) or para-aminohippuric acid clearance (CPAH), whereas urinary thromboxane excretion was suppressed. Only the administration of the selective blockers imidazole and dazoxiben resulted in a marked increase in urinary volume (V) and fractional sodium excretion (FENa). HgCl2 alone (2 mg/kg i.v.) caused a decrease in GFR and CPAH with –38% (P<0.01), and urinary thromboxane B2 excretion increased from 20.3±1.5 to 30.6±2.6 pg/min. (P<0.01). The administration of indomethacin, imidazole (50 µmol/kg per min) and dazoxiben prevented the increase in thromboxane B2 excretion 3 h after HgCl2 to values of 3.3±1.2, 6.9±0.6 and 13.0±1.6 pg/min respectively (P<0.01 versus control for all values). Despite this, the decrease in GFR and CPAH after HgCl2 could not be prevented. A decrease of GFR with –44, –54, –57 and –32% and of CPAH with –37, –49, –57 and –27% were observed for indomethacin, imidazole 25 and 50 µmol/kg per min and dazoxiben respectively. This evolution was not significantly different from what was observed with mercury alone. Selective thromboxane synthesis inhibition resulted in a decrease of serum free ionised calcium. We conclude that in the rat there is no relationship between the inhibition of thromboxane synthesis after HgCl2 on the one hand and the evolution of HgCl2-induced acute renal failure on the other. The thromboxane system does not play a major pathophysiological role in the early phase of toxic acute renal failure.
Keywords: Acute renal failure (toxic); Dazoxiben; Imidazole; Indomethacin; Mercury chloride; Prostaglandins; Thromboxane
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