Attenuation of nephrotoxic acute renal failure in the dog with angiotensin-converting enzyme inhibitor (SQ-20,881).
Angiotensin-converting enzyme inhibitor was used in dogs with uranyl nitrate-induced acute renal failure to evaluate (1) a possible protective effect of angiotensin blockade and (2)the role of angiotensin II in the generation of renal failure in this model. Angiotensin-converting enzyme inhibitor treatment attenuated the fall in glomerular filtration rate and renal blood flow during the first 6 hours after injection of the nephrotoxic agent. A protective effect of similar magnitude was observed whether angiotensin-converting enzyme inhibitor treatment preceded, or shortly followed, the administration of uranyl nitrate. This indicates that angiotensin-converting enzyme inhibitor delivery to its intrarenal site of action remains effective after administration of the nephrotoxin. In addition, protection of glomerular filtration rate correlated with sodium and renal solute excretion. However, combined treatment with angiotensin-converting enzyme inhibitor and furosemide enhanced solute excretion but did not further improve the protection of renal function. Finally, the protective effects of angiotensin-converting enzyme inhibitor on renal function and hemodynamics were abolished by intravenous indomethacin. In conclusion, early, continuous blockade of angiotensin II protects partially against th initiation of acute renal failure. These findings support a major pathogenic role for angiotensin II in the generation phase of acute renal failure in this model. Furthermore, they suggest that an imbalance between vasoconstrictive (angiotensin II) and vasodilating factors (prostaglandins) may be operative in the early phase of uranyl nitrate-induced acute renal failure in the dog.
D058186:Acute Kidney Injury / Q000503:physiopathology*; D000818:Animals; D004285:Dogs; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects*; D008297:Male; D009842:Oligopeptides / Q000633:toxicity*; D013722:Teprotide / Q000494:pharmacology / Q000633:toxicity*
D009842:Oligopeptides; D013722:Teprotide; D007213:Indomethacin