Vemulapalli S, Chiu P J, Chintala M, Bernardino V
Schering-Plough Research Institute, Kenilworth, NJ 07033-0539.
Pharmacology. 1993 Sep;47(3):188-93. doi: 10.1159/000139096.
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.
在麻醉大鼠中研究了内皮素转化酶和中性内肽酶（E.C. 24.11）的双重抑制剂磷酰胺素对缺血性急性肾衰竭肾功能的保护作用。静脉输注磷酰胺素（每分钟0.03和0.1毫克/千克）可显著抑制缺血后肾脏的肾小管钠排泄（通过钠分数排泄来测量）和蛋白尿，而对侧正常肾脏的功能参数未发生改变。磷酰胺素（每分钟0.1毫克/千克）可使缺血肾脏的肾小球滤过增加。相比之下，高选择性中性内肽酶抑制剂SCH 42354在每分钟0.3毫克/千克时，既不抑制内皮素转化酶，也不提供肾脏保护。数据表明，磷酰胺素对缺血性急性肾衰竭的保护作用很可能是通过抑制内皮素的形成介导的。
