The mechanism and treatment of ischemic acute renal failure -rde of superoxide -

实验室调查。白三烯D_4 (LTD_4)，刺激超氧化物，减少肾血浆流量和肾小球滤过率可能通过收缩肾小球系膜细胞。心房利钠因子（ANF）通过放松系膜细胞增加肾血浆流量和肾小球滤过率。我们研究了肾小球LTD_4和ANF之间的相互作用。ANF刺激大鼠肾小球剂量依赖性cGMP的产生。LTD_4抑制大鼠肾小球中anf依赖性cGMP的产生。LTD_4可能至少部分通过抑制cGMP的产生而降低肾功能。2. 由于该方法的灵敏度限制，无法从鲍曼胶囊直接获得的样品中测量超氧化物的量。3. 内皮素是一种由受损的内皮细胞通过超氧化物分泌而降低肾功能的肽。该肽在缺血性急性肾功能衰竭的发病机制中起重要作用。我们研究了内皮素和几种多肽之间的相互作用。我们的研究结果表明，内皮素选择性地抑制avp依赖性cAMP在集管中的产生。因此，内皮素可以通过增加尿量来抵消肾小球滤过率的下降。临床研究。1. 甲状腺激素，可能刺激超氧化物在肾脏，研究急性肾功能衰竭。急性肾功能衰竭致死性组甲状腺激素水平较低，可能是调节其减少而不是增加超氧化物。2. 内皮素在急性肾功能衰竭时由受损的内皮细胞分泌，在急性肾功能衰竭的急性期升高，随着肾功能的恢复而降低。提示内皮素与急性肾功能衰竭患者肾功能不全有一定关系。

Laboratory Investigation. 1. Leukotriene D_4 (LTD_4), which stimulates superoxide, reduces renal plasma flow and glomerular filtration rate possibly by contracting mesangial cells in glomerulus. Atrial natriuretic factor (ANF), on the other hand, increases renal plasma flow and glomerular filtration rate through relaxing mesangial cell. We investigated the interaction between LTD_4 and ANF in glomerulus. ANF stimulates dose- dependently cGMP production in rat glomerulus. LTD_4 inhibited ANF-dependent cGMP production in rat glomerulus. LTD_4 possibly decreases renal function at least in part by inhibiting the production of cGMP. 2. It could not be possible to measure the amount of superoxide from the sample directly obtained through bowmann's capsule mainly because the sensitivity limits of the method. 3. Endothelin is a peptide which could be secreted from damaged endothelial cells by superoxide, and decrease renal function. This peptide is very important in the pathogenesis of ischemic acute renal failure. We investigated the interaction between endothelin and several peptides. Our results suggest that endothelin selectively inhibits AVP-dependent cAMP production in collecting ducts. Thus, endothelin will counteract the decrease in glomerular filtration rate by increasing in urine volume.Clinical study. 1. Thyroid hormone, which probably stimulates superoxide in the kidney, was investigated in acute renal failure. Fatal group of acute renal failure has lower level of thyroid hormone, which might be regulated to decrease not to increase superoxide. 2. Endothelin, which could be secreted by damaged endothelial cells in acute renal failure, is increased in the acute stage of acute renal failure and decreased with the recovery in renal function. This results suggest some relation between endothelin and renal dysfunction in acute renal failure.