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

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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.