Reversibility of acute cyclosporin nephrotoxicity by dopamine. Micropuncture study in the rat.
The ability of dopamine to neutralise the effects acutely induced by cyclosporin (CsA) on glomerular dynamics was evaluated in four groups of female Munich-Wistar rats, prepared for micropuncture: group I (n = 9), normal rats receiving saline as placebo; group II (n = 10), rats treated with CsA (20 mg/kg b.w. in 1 h); group III (n = 8) rats treated with CsA, as in group II, and then with vasodilating doses of dopamine (1.2-2.0 micrograms/100 g b.w./min in continuous intravenous infusion); group IV (n = 7), rats administered Cremophore EL, the vehicle of CsA, in corresponding doses. Single nephron GFR (SNGFR), glomerular plasma flow (GPF), afferent and efferent arteriole resistances (Ra and Re, respectively), SN filtration fraction (SNFF), ultrafiltration coefficient (Kf) were measured. Body weight, blood pressure and haematocrit were similar in the four groups. GFR was significantly reduced in group II (0.83 +/- 0.08 ml/min vs 1.29 +/- 0.01 in group I, 1.46 +/- 0.25 in group III, and 1.40 +/- 0.09 in group IV, P less than 0.05 vs all the groups), while no statistical difference was detected in urinary volume. SNGFR was significantly reduced in group II vs group I (18.7 +/- 1.8 nl/min vs 30.6 +/- 1.3, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Sabbatini
M
M
Department of Nephrology, 2nd Faculty of Medicine, University of Naples, Italy.
Esposito
C
C
De Nicola
L
L
Uccello
F
F
Altomonte
M
M
Conte
G
G
Dal Canton
A
A
Andreucci
V E
VE
D000818:Animals; D003524:Cyclosporins / Q000633:toxicity*; D004298:Dopamine / Q000494:pharmacology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D005990:Glycerol / Q000031:analogs & derivatives / Q000633:toxicity; D007262:Infusions, Intravenous; D007676:Kidney Failure, Chronic / Q000139:chemically induced*; D014677:Pharmaceutical Vehicles; D051381:Rats; D011919:Rats, Inbred Strains
D003524:Cyclosporins; D014677:Pharmaceutical Vehicles; C000515:cremophor EL; D005990:Glycerol; D004298:Dopamine