Influence of nifedipine on cyclosporin A nephrotoxicity after unilateral nephrectomy in the spontaneously hypertensive rat.
1. Nifedipine ameliorates cyclosporin A-induced renal impairment in surgically intact (two-kidney) rats. This study investigates the effect of nifedipine on cyclosporin A nephrotoxicity in spontaneously hypertensive rats after either uninephrectomy or uninephrectomy with contralateral renal denervation. 2. Fourteen days after uninephrectomy pair-fed rats were injected for 14 days with cyclosporin A (25 mg/kg body weight) via the subcutaneous route and with nifedipine (0.1 mg/kg body weight) via the intraperitoneal route. Renal and systemic haemodynamics were measured in conscious unrestrained rats. 3. Whole-blood levels of cyclosporin A did not differ between groups (overall 352 +/- 22 ng/ml, means +/- SEM). After uninephrectomy, cyclosporin A decreased the glomerular filtration rate (olive oil versus cyclosporin A: 0.96 +/- 0.04 versus 0.70 +/- 0.06 ml min-1 100 g body weight, P less than 0.02) and effective renal plasma flow (1.94 +/- 0.10 versus 1.38 +/- 0.13, P less than 0.01), and increased renal vascular resistance [(20.2 +/- 1.8) x 10(4) versus (31.6 +/- 3.3) x 10(4) kPa l-1 s [(20.2 +/- 1.8) x 10(3) versus (31.6 +/- 3.3) x 10(3) dyn s cm-5], P less than 0.02] and mean arterial pressure (146.7 +/- 6.7 versus 167.3 +/- 2.9 mmHg, P less than 0.05). Neither renal denervation nor nifedipine prevented the reduction in glomerular filtration rate or effective renal plasma flow induced by cyclosporin A. 4. This study infers that the sympathetic nervous system does not play an active role in cyclosporin A nephrotoxicity and demonstrates that the concomitant administration of nifedipine to rats with reduced renal mass does not ameliorate cyclosporin A-induced renal impairment.
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 / Q000009:adverse effects*; D003714:Denervation; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000294:innervation; D007674:Kidney Diseases / Q000517:prevention & control*; D009392:Nephrectomy; D009543:Nifedipine / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D003524:Cyclosporins; D009543:Nifedipine