The effects of nifedipine on cyclosporine nephrotoxicity in rats.
We have investigated the effect of nifedipine on cyclosporine nephrotoxicity in the Sprague-Dawley rat employing a repeatable, single-shot, isotopic technique of measuring the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). Groups of 10 rats received either cyclosporine 5 mg/kg daily or cremaphor with either nifedipine 0.5 mg/kg daily or its vehicle for 14 days. In the cyclosporine group the GFR (P < 0.001, paired t-test), ERPF and filtration fraction (FF) (P < 0.01) all fell significantly. The cyclosporine plus nifedipine group underwent an increase in the ERPF (P < 0.01), the GFR remained unchanged, and the FF fell significantly (P < 0.0001). In this model, nifedipine completely abolished the renal arteriolar vasospasm produced by cyclosporine. That the FF fell in the cyclosporine plus nifedipine-treated animals indicates that cyclosporine has an effect which is not mediated by arteriolar vasoconstriction. This action may be at the glomerular level and is resistant to calcium channel blockade.
Ferguson
C J
CJ
Department of Surgery and Institute for Nephrology, Cardiff Royal Infirmary, Cardiff, United Kingdom.
von Ruhland
C
C
Parry-Jones
D J
DJ
Williams
J D
JD
Salaman
J R
JR
D000818:Animals; D016572:Cyclosporine / Q000633:toxicity*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D007668:Kidney / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D008297:Male; D023421:Models, Animal; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D016572:Cyclosporine; D009543:Nifedipine