Effect of nifedipine on renal haemodynamics in an animal model of cyclosporin A nephrotoxicity.
1. This study investigates the effect of nifedipine on cyclosporin A nephrotoxicity in the spontaneously hypertensive rat. 2. Cyclosporin A, administered daily by subcutaneous injection at 25 mg/kg body weight for 14 days, induced a significant reduction in glomerular filtration rate (35.3%) and effective renal plasma flow (45.0%), and an increase in renal vascular resistance (219%). Using this regimen, tubular, glomerular or vascular morphological damage was not evident on light microscopy. 3. The administration of nifedipine simultaneously with cyclosporin A from day 1 prevented the characteristic decline in renal function and increase in renal vascular resistance. However, the administration of nifedipine to spontaneously hypertensive rats previously exposed to cyclosporin A for 7 days failed to improve renal haemodynamics. 4. This study suggests that the beneficial effect conferred by nifedipine on cyclosporin A nephrotoxicity is present only when treatment is initiated simultaneously with cyclosporin A.
McNally
P G
PG
Department of Nephrology, Leicester General Hospital, U.K.
Baker
F
F
Mistry
N
N
Walls
J
J
Feehally
J
J
D000818:Animals; D003524:Cyclosporins / Q000633:toxicity*; D004195:Disease Models, Animal; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D007674:Kidney Diseases / Q000139:chemically induced*; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D014655:Vascular Resistance / Q000187:drug effects
D003524:Cyclosporins; D009543:Nifedipine