The relative role of thromboxane (TxA2) and sulfido-peptide 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 (P2 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.
|Number of pages||6|
|Publication status||Published - 1991|
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