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-iodinated ionic contrast media, Hypaque, was evaluated in anesthetized dogs in the presence or absence of the cyclooxygenase inhibitor, indomethacin (10 mg/kg, i.v.). Hypaque alone (5 ml/kg, i.v.) resulted in a marked diuresis and natriuresis but little change in either renal blood flow 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 increase in renal vascular resistance which was abolished by (+/-)-SB 209670. The data indicate that the radiocontrast media, Hypaque, can cause renal vasoconstriction which may be mediated by ET.
Brooks
D P
DP
Department of Renal Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939 USA.
DePalma
P D
PD
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003287:Contrast Media / Q000009:adverse effects*; D004231:Diuresis / Q000187:drug effects; D004285:Dogs; D065128:Endothelin Receptor Antagonists; D005260:Female; D005919:Glomerular Filtration Rate; D007189:Indans / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000517:prevention & control* / Q000652:urine; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
D003287:Contrast Media; D065128:Endothelin Receptor Antagonists; D007189:Indans; C087551:1H-Indene-2-carboxylic acid, 1-(1,3-benzodioxol-5-yl)-3-(2- (carboxymethoxy)-4-methoxyphenyl)-2,3-dihydro-5-propoxy-, (1S,2R,3S)-