Bosentan, an orally active endothelin antagonist: effect on the renal response to contrast media.
OBJECTIVE
To examine the effect of bosentan, an orally active endothelin-receptor antagonist, on the renal response to contrast media in the isolated perfused rat kidney (IPRK) and to establish whether bosentan can inhibit contrast media-induced nephrotoxicity in a multiple-insult model in the conscious rat.


METHODS
Renal function was measured in the IPRK (n = 24) and in the rats that had undergone unilateral nephrectomy, were maintained on a salt-free diet, and were receiving indomethacin (10 mg/kg/d; n = 60).


RESULTS
In the IPRK, diatrizoate and iotrolan reduced the glomerular filtration rate and renal perfusate flow, an effect markedly inhibited by bosentan (n = 6 per group). In the multiple-insult rat model, the fall in creatinine clearance produced by diatrizoate was also markedly inhibited by bosentan (n = 15 per group).


CONCLUSIONS
Endothelin antagonists such as bosentan may be used to reduce the prevalence of contrast-induced nephrotoxicity.
Oldroyd
S D
SD
Sheffield Kidney Institute, Northern General Hospital, Sheffield, England.
Haylor
J L
JL
Morcos
S K
SK
D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D000077300:Bosentan; D003287:Contrast Media / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood / Q000652:urine; D003973:Diatrizoate / Q000009:adverse effects; D004039:Diet, Sodium-Restricted; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D007444:Inulin / Q000652:urine; D007668:Kidney / Q000187:drug effects*; D008297:Male; D009392:Nephrectomy; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D014283:Triiodobenzoic Acids / Q000009:adverse effects
D003287:Contrast Media; D065128:Endothelin Receptor Antagonists; D013449:Sulfonamides; D014283:Triiodobenzoic Acids; D003973:Diatrizoate; C033300:iotrolan; D007444:Inulin; D003404:Creatinine; D000077300:Bosentan; D007213:Indomethacin