METABOLISM OF ENDOTHELIN

内皮素的代谢

• 批准号: 3858084
• 负责人: Z ABASSI
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3858084
• 关键词: high performance liquid chromatography; hypertension; laboratory rat; nephrectomy; peptides; protein metabolism; radiotracer; vasoconstrictors

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.

内皮素 (ET) 是内皮源性血管收缩剂 血管内皮细胞在各种情况下产生和释放的肽 物理和化学刺激。 我们研究了 1) 尿液排泄和血浆水平 对照大鼠和用中性肽链内切酶预处理的大鼠中的 ET 抑制剂（NEP-1）SQ29,072。 2).NEP-1对命运的影响 使用高效液相色谱法注入 125-I-ET。 3) 的 双侧肾切除术或 NEP-1 给药对 抑制剂活性或输注 ET。 NEP-1（30 和 60 ng/kg）显着增加尿 内皮素在 30、60 和 90 分钟时排泄。 此外， 更高剂量的 NEP-1 使血浆 ET 水平升高 55%。 之后 将 125-I-ET 输注至对照大鼠体内，放射性恢复 尿液可以忽略不计，而在 NEP-1 存在的情况下，放射性 增加了3倍。 此外，对回收的放射性进行分析 HPLC 显示完整的 ET 占总计数的 6-9% 对照大鼠，而在用抑制剂预处理的大鼠中，该值 增加到50-60%。 双侧肾切除术与增强和 延长 ET 的高血压作用。 抑制 NEP 增强 ET 的抑制活性，其方式类似于 在双侧肾切除大鼠中获得的结果。