Abstract |
The relative role of thromboxane (TxA2) and sulfidopeptide leukotrienes C4 ( LTC4) and D4 ( LTD4) in the acute renal failure induced by cyclosporine was studied in the rats. Bolus i.v. administration of 20 mg/kg of CsA but not vehicle to adult male Sprague-Dawley rats resulted in a significant fall in glomerular filtration rate from 0.85 +/- 0.10 and renal plasma flow (RPF) 2.45 +/- 0.14 ml/min/100 g body wt to values at 20 min of 0.47 +/- 0.03 and 1.01 +/- 0.12 ml/min/100 g body wt (P less than 0.01), respectively, without a fall in mean arterial pressure. This hemodynamic effect was maintained for the following 40-min period. Pretreatment of rats with the TxA2 receptor antagonist GR32191 (3 mg/kg i.v.) allowed a partial but significant preservation of GFR (0.60 +/- 0.05 ml/min/100 g body wt) and RPF (1.55 +/- 0.12 ml/min/100 g body wt). In addition, the antagonism of endogenously produced LTC4 and LTD4 with the putative receptor antagonist L-649,923 (1 mg/kg i.v.) partially prevented the fall in GFR (0.65 +/- 0.07 ml/min/100 g body wt) and RPF (1.80 +/- 0.18 ml/min/100 g body wt) at 20 min after CsA injection. The combined administration of GR32191 and L-649,923 completely abolished the CsA-induced decline in GFR (0.80 +/- 0.09 ml/min/100 g body wt) and RPF (2.40 +/- 0.12 ml/min/100 g body wt). These findings suggest that TxA2 and LTC4/ LTD4 participate in mediating renal function deterioration induced by acute CsA administration in the rat.
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Authors | N Perico, M Pasini, F Gaspari, M Abbate, G Remuzzi |
Journal | Transplantation
(Transplantation)
Vol. 52
Issue 5
Pg. 873-8
(Nov 1991)
ISSN: 0041-1337 [Print] United States |
PMID | 1835198
(Publication Type: Journal Article)
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Chemical References |
- Biphenyl Compounds
- Heptanoic Acids
- Phenylbutyrates
- Receptors, Prostaglandin
- Receptors, Thromboxane
- SRS-A
- Thromboxane A2
- Cyclosporine
- L 649923
- vapiprost
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Topics |
- Acute Kidney Injury
(chemically induced)
- Analysis of Variance
- Animals
- Biphenyl Compounds
(pharmacology)
- Blood Pressure
(drug effects)
- Cyclosporine
(adverse effects, pharmacokinetics)
- Drug Antagonism
- Glomerular Filtration Rate
(drug effects)
- Heptanoic Acids
(pharmacology)
- Injections, Intravenous
- Kidney
(blood supply, metabolism)
- Male
- Metabolic Clearance Rate
- Phenylbutyrates
(pharmacology)
- Rats
- Rats, Inbred Strains
- Receptors, Prostaglandin
(antagonists & inhibitors)
- Receptors, Thromboxane
- SRS-A
(antagonists & inhibitors, physiology)
- Thromboxane A2
(physiology)
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