METABOLISM OF ENDOTHELIN

内皮素(ET)是一种内皮来源的血管收缩因子 血管内皮细胞在多种细胞表面产生和释放的多肽 物理和化学刺激。 我们调查了1)尿排泄量和血浆中 正常大鼠和中性内肽酶预处理大鼠的ET变化 抑制剂(NEP-1)SQ29,072。2).NEP-1对细胞命运的影响 用高效液相色谱法输注~(125)I-ET。3) 双侧肾切除或应用NEP-1对大鼠肾功能的影响 降压活动或输注ET。 NEP-1(30和60 ng/kg)可显著增加小鼠的尿量 30分钟、60分钟和90分钟的内皮素排泄量。此外， 高剂量的NEP-1可使血浆ET水平升高55%。后 125I-ET对正常大鼠脑内放射性恢复的影响 在NEP-1存在的情况下，尿液的放射性可以忽略不计 增加了3倍。此外，对恢复的放射性进行了分析 经高效液相色谱检测表明，完整的ET占总计数的6%-9% 对照组大鼠，而在用抑制剂预处理的大鼠中 增加到50%-60%。 双侧肾切除与增强和 延缓ET的降压作用。抑制 NEP增强ET的降压活性的方式类似于 在双侧肾切除大鼠中获得的。

Endothelins (ET's) are endothelium-derived vasoconstrictor peptides produced and released by vascular endothelial cells upon various physical and chemical stimuli. We investigated 1) the urinary excretion and plasma levels of ET in control rats and rats pretreated with the neutral endopeptidase inhibitor (NEP-1) SQ29,072. 2).The effects of NEP-1 on the fate of infused 125-I-ET using high performance liquid chromatography. 3) The effect of either bilateral nephrectomy or administration of NEP-1 on the depressor activity or infused ET. NEP-1 (30 and 60 ng/kg) significantly increased the urinary excretion of endothelin at 30, 60 and 90 minutes. In addition, the higher dose of NEP-1 elevated plasma levels of ET by 55%. After the infusion of 125-I-ET into control rats, the recovery of radioactivity in the urine was negligible, while in the presence of NEP-1, radioactivity increased 3 fold. Furthermore, analysis of the recovered radioactivity by HPLC revealed that intact ET comprised 6-9% of the total counts in control rats, while in rats pretreated with the inhibitor that value increased to 50-60%. Bilateral nephrectomy was associated with potentiation and prolongation of the hypertensive effect of administered ET. Inhibition of NEP potentiated the depressor activity of ET in a manner similar to that obtained in bilateral nephrectomized rats.