Antagonist capacity of felodipine on cyclosporin A nephrotoxicity in the rat.
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 microliters/min per g kidney weight (KW), P < 0.05) and CLi (130 versus 271 microliters/min per gKW, P < 0.02). Felodipine decreased proximal fractional reabsorption (PFR) (67.5% versus 71.4%, P < 0.05) and increased CNa (15.9 versus 8.4 microliters/min per gKW, P < 0.02) as compared to controls. In CsA-treated rats felodipine increased C in (1260 versus 730 microliters/min per gKW, P < 0.05) and CLi (319 versus 130 microliters/min per gKW, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
Dieperink
H
H
Laboratory of Nephropathology, Odense University Hospital, Denmark.
Hansen
H V
HV
Kemp
M
M
Leyssac
P P
PP
Starklint
H
H
Kemp
E
E
D000042:Absorption; D000704:Analysis of Variance; D000818:Animals; D016572:Cyclosporine / Q000037:antagonists & inhibitors* / Q000633:toxicity; D015736:Felodipine / Q000494:pharmacology*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D016572:Cyclosporine; D015736:Felodipine