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

实验室调查。1.白三烯D_4(LTD_4)刺激超氧化物歧化，可能通过收缩肾小球系膜细胞减少肾血浆流量和肾小球滤过率。另一方面，心钠素(ANF)通过松弛系膜细胞而增加肾血浆流量和肾小球滤过率。我们研究了LTD_4与肾小球ANF的相互作用。ANF呈剂量依赖性地刺激大鼠肾小球cGMP的产生。LTD_4抑制大鼠肾小球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.由于方法的灵敏度限制，不能直接从鲍曼胶囊获得的样品中测定超氧化物歧化酶的含量。3.内皮素是一种可由超氧化物损伤的内皮细胞分泌的多肽，可降低肾功能。该肽在缺血性急性肾功能衰竭的发病机制中起重要作用。我们研究了内皮素与几种多肽之间的相互作用。我们的结果表明，内皮素选择性地抑制集合管中依赖于AVP的cAMP的产生。因此，内皮素将通过增加尿量来抵消肾小球滤过率的下降。临床研究。1.探讨了急性肾功能衰竭时甲状腺激素对肾脏超氧化物歧化的刺激作用。急性肾功能衰竭致死组甲状腺激素水平较低，可调节为降低而不是升高超氧阴离子。2.急性肾功能衰竭时受损内皮细胞分泌的内皮素在急性肾功能衰竭急性期升高，并随肾功能恢复而降低。提示内皮素与急性肾功能衰竭时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.