Attenuation of ischemic acute renal failure by phosphoramidon in rats.
The protective effects of phosphoramidon, a dual inhibitor of endothelin-converting enzyme and neutral endopeptidase (E.C. 24.11), on renal function in ischemic acute renal failure were investigated in anesthetized rats. Intravenous infusion of phosphoramidon (0.03 and 0.1 mg/kg per min) significantly suppressed tubular sodium wasting (measured by fractional excretion of sodium) and proteinuria in the postischemic kidney without modifying functional parameters in the contralateral normal kidney. Phosphoramidon (0.1 mg/kg/min) was associated with increased glomerular filtration in the ischemic kidney. In comparison, SCH 42354, a highly selective inhibitor of neutral endopeptidase at 0.3 mg/kg/min, did not inhibit endothelin-converting enzyme or afford renal protection. The data suggest that the protective action of phosphoramidon against ischemic acute renal failure is most likely mediated by inhibition of endothelin formation.
Vemulapalli
S
S
Schering-Plough Research Institute, Kenilworth, NJ 07033-0539.
Chiu
P J
PJ
Chintala
M
M
Bernardino
V
V
D058186:Acute Kidney Injury / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D004195:Disease Models, Animal; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000378:metabolism; D005919:Glomerular Filtration Rate; D006020:Glycopeptides / Q000494:pharmacology / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D008666:Metalloendopeptidases; D008715:Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D051381:Rats
D016232:Endothelins; D006020:Glycopeptides; C086374:CGS 26129; D008715:Methionine; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D015260:Neprilysin; D000072396:Endothelin-Converting Enzymes; C008890:phosphoramidon