Blockade of Radiocontrast-lnduced Nephrotoxicity by the Endothelin Receptor Antagonist, SB 209670

Abstract

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.

Endothelin and Tubulointerstitial Renal Disease

“…29,30 Contrast media can directly damage endothelial cells in renal vessels, 31 which may explain the observed increase in ET-1 levels. Administration of ET-receptor antagonists prevented renal vasoconstriction 32,33 as well as improved functional and structural markers [32][33][34][35][36] in animal models of radiocontrast nephrotoxicity ( Table 2).…”

Clinical and Experimental Evidence for Prevention of Acute Renal Failure Induced by Radiographic Contrast Media

“…In addition, RCM stimulate the release of endothelin from cultured bovine aortic endothelial cells, in which the extent of endothelin release is correlated with the renal toxicity of RCM assessed by the decrease in creatinine clearance and morphologic damage (65). On the other hand, the decrease in renal blood flow and increase in renal vascular resistance induced by intravenous RCM injection in anesthetized dogs pretreated with indomethacin are reversed by the non-selective endothelin antagonist SB 209670 (66). Moreover, the decrease in PaO 2 induced by RCM in the rat outer medulla is reversed by the selective ETA antagonist BQ123 (52).…”

Contrast Medium‐Induced Nephrotoxicity: Pathophysiology and Prevention

“…4,19 Although a variety of substances may mediate this vasoconstrictive response, adenosine and endothelin seem to be the most prevalent and responsible. 4,9,22,23 Vasoconstriction not only causes a decrease in renal blood flow and glomerular filtration rate, it exacerbates medullary ischemia by decreasing oxygen supply ( Figure 1).…”