Upregulation of renal endothelin receptors in rats with cyclosporine A-induced nephrotoxicity.
Measurement of endothelin receptors by binding assay was performed in rats treated with cyclosporine A (CYA). Cyclosporine A administration at 50 mg/kg i.p. for 4 days resulted in renal function impairment as indicated by a significant increase in serum creatinine concentration (from 0.46 +/- 0.02 to 0.61 +/- 0.03 mg/dl. P less than 0.01) and a significant decrease in 24 h creatinine clearance (from 0.65 +/- 0.04 to 0.41 +/- 0.02 ml/min per 100 g, P less than 0.01). Renal endothelin (ET) receptor density was significantly higher in CYA-treated rats (312 +/- 34 vs. 196 +/- 26 fmol/mg protein, P less than 0.01). These data support the possible involvement for endothelin in the increased renal vascular resistance associated with CYA-induced nephrotoxicity.
Nambi
P
P
SmithKline Beecham Pharmaceuticals, Department of Pharmacology, King of Prussia, PA 19406-0936.
Pullen
M
M
Contino
L C
LC
Brooks
D P
DP
D000818:Animals; D003404:Creatinine / Q000097:blood; D003524:Cyclosporins / Q000633:toxicity*; D007457:Iodine Radioisotopes; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017466:Receptors, Endothelin; D015854:Up-Regulation / Q000187:drug effects*
D003524:Cyclosporins; D007457:Iodine Radioisotopes; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D003404:Creatinine