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- Title
Antagonist capacity of felodipine on cyclosporin A nephrotoxicity in the rat.
- Authors
Dieperink, H.; Hansen, H. V.; Kemp, M.; Leyssac, P. P.; Starklint, H.; Kemp, E.
- Abstract
Functional and morphological cyclosporin A (CsA) nephropathy has been attributed to a CsA-induced constriction of the afferent glomerular arteriole. Calcium-channel blockade with nifedipine prevented the development of short-term functional nephrotoxicity in CsA-treated rats. This study investigated whether the calcium antagonist felodopine a structural analogue of nifedipine which reduces renal tubular fractional sodium reabsorption could prevent both short- and long-term functional and long-term morphological CsA nephropathy. In short-term experiments four groups of Spraque-Dawley rats (n = 39) were given CsA (either 0 or 12.5 mg/kg per day by daily gastric intubation for 2 weeks) and felodipine (0 or 30 mg/kg per day) in the diet. In long-term experiments rats (n = 39) were given CsA (12.5 mg/kg per day for 16 weeks) and felodipine (0 or 30 mg/kg per day in the diet). Renal function was investigated with clearance methods (inulin lithium and sodium) and kidney morphology was studied by light-microscopy. In short-term experiments CsA treatment reduced GFR (730 versus 1181 μl/min per g kidney weight (KW) P<0.05) and C< (130 versus 271 μl/min per gKW P<0.02). Felodipine decreased proximal fractional reabsorption (PFR) (67.5% versus 71.4% p<0.05) and increased C (15.9 versus 8.4 μl/min per gKW p<0.02) as compared to controls. In CsA-treated rats felodipine increased C (1260 versus 730 μl/min per gKW p<0.05) and C (319 versus 130 μlsol;min per gKW P<0.02). Also in long-term experiments felodipine given to CsAtreated rats increased C (1361 versus 956 μl/min per gKW p<0.05) and C (246 versus 146 μl/min per gKW p<0.05). Felodipine did not reduce the number of collapsed basophilic tubules or the amount of interstitial fibrosis in the kidneys from CsA-treated rats. In conclusion short- and long-term co-treatment with felodipine and CsA reduced functional CsA nephrotoxicity. Felodipine was unable to prevent CsA-induced morphological damage to the kidneys.
- Publication
Nephrology Dialysis Transplantation, 1992, Vol 7, Issue 11, p1124
- ISSN
0931-0509
- Publication type
Article