Research of the mechanism and treatment for acute renal failure-role of endothelin-

基本的所。探讨内皮素在大鼠急性肾功能衰竭发生机制中的作用。双侧肾动脉夹持45分钟后肾小球滤过率持续下降。测定肾动脉夹持后第2天血浆内皮素水平。肾小管悬浮液中内皮素含量在第2天也有所增加。实验表明，经胎牛血清和转化生长因子- β孵育后，肾小管悬浮液中内皮素含量增加。这些数据提示内皮素可能在急性肾功能衰竭等组织损伤的情况下通过转化生长因子- β在肾髓质中合成。本文探讨了内皮素在体液平衡调节中的作用，特别是在容量过载状态下，如急性肾功能衰竭引起的肾功能下降。内皮素降低avp依赖性cAMP在微解剖大鼠集管中的积累。在微灌注实验中，内皮素还能抑制avp依赖性大鼠收集管的水和氯离子重吸收。因此，内皮素在急性肾功能衰竭等容量过载状态下具有利尿作用。临床研究：急性肾功能衰竭患者血浆内皮素水平升高。随着肾功能的恢复，它们逐渐减少。部分病例显示血浆内皮素水平升高先于血清Cr水平升高。这也提示内皮素在肾功能恶化中的作用。

BASIC STUDY1. I investigated the role of endothelin in the mechanisms of acute renal failure in rat. Decreases in glomerular filtration rate persisted after 45 minutes clamp of bilateral renal artery. Plasma endothelin levels showed the value at the 2nd day after clamp of renal artery. Endothelin content of renal tissue also increased at 2nd day Renal tubule suspension experiments showed that endothelin production increased in renal medullary tubule suspension after incubation with fetal calf serum and transforming growth factor -BETA. These data suggest that endothelin was synthesized in renal medulla by transforming growth factor - BETA possibly in cases of tissue damage such as acute renal failure.2. Role of endothelin in the regulation of body fluid homeostasis was investigated especially in the state of volume overload such as decrease in renal function due to acute renal failure. Endothelin decreased AVP-dependent cAMP accumulation in microdissected rat collecting duct. In microperfusion experiments, endothelin also inhibited AVP-dependent water and chloride reabsorption in rat collecting duct. Therefore endothelin has roles to induce diuresis in the state of volume overload such as acute renal failure.CLINICAL STUDYPlasma endothelin levels were increased in acute renal failure. They decreased following the recovery of renal function. Some case showed that raises in plasma endothelin level preceded the increase in serum Cr levels. This also suggest the role of endothelin in deterioration of renal function.