BLOCKADE OF RADIOCONTRAST-INDUCED NEPHROTOXICITY BY THE ENDOTHELIN RECEPTOR ANTAGONIST, SB-209670

The effect of the novel nonpeptide endothelin (ET) receptor antagonist , (+/-)-SB 209670, on the renal effects of the high osmolar tri-iodina ted ionic contrast media, Hypaque, was evaluated in anesthetized dogs in the presence or absence of the cyclooxygenase inhibitor, indomethac in (10 mg/kg, i.v.). Hypaque alone (5 ml/kg, i.v.) resulted in a marke d diuresis and natriuresis but little change in either renal blood flo w or renal vascular resistance. When the ET receptor antagonist, (+/-) -SB 209670, was infused into the renal artery at a dose that inhibited ET-induced renal vasoconstriction, Hypaque resulted in a significant increase in renal blood flow and decrease in renal vascular resistance . In the presence of indomethacin, Hypaque caused a significant increa se in renal vascular resistance which was abolished by (+/-)-SB 209670 . The data indicate that the radiocontrast media, Hypaque, can cause r enal vasoconstriction which may be mediated by ET.