Effect of nifedipine on cyclosporine A-induced nephrotoxicity, urinary endothelin excretion and renal endothelin receptor number.
The aim of the present study was to determine the effect of a calcium channel blocker on renal function, urinary endothelin excretion and endothelin receptor number in rats. Administration of cyclosporine resulted in a significant impairment of renal function when measured by either [14C]inulin or 24 h creatinine clearances. This nephrotoxicity was associated with statistically significant (P less than 0.05) increases in urinary endothelin excretion and renal endothelin receptor number. Treatment with nifedipine attenuated cyclosporine A-induced renal dysfunction and reduced urinary endothelin excretion. The data provide further evidence of a role for endothelin in cyclosporine A-induced nephrotoxicity.
Brooks
D P
DP
SmithKline Beecham Pharmaceuticals, Department of Pharmacology, King of Prussia, PA 19406-0939.
Ohlstein
E H
EH
Contino
L C
LC
Storer
B
B
Pullen
M
M
Caltabiano
M
M
Nambi
P
P
D000818:Animals; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D003524:Cyclosporins / Q000633:toxicity*; D016232:Endothelins / Q000652:urine*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007674:Kidney Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D017466:Receptors, Endothelin
D003524:Cyclosporins; D016232:Endothelins; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D003404:Creatinine; D009543:Nifedipine