ANGIOTENSIN-II AUGMENTS MEDULLARY HYPOXIA AND PREDISPOSES TO ACUTE-RENAL-FAILURE
ANGIOTENSIN-II AUGMENTS MEDULLARY HYPOXIA AND PREDISPOSES TO ACUTE-RENAL-FAILURE
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DOI：
10.1111/j.1365-2362.1990.tb02269.x
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发表时间：
1990-04-01
影响因子：
5.5
通讯作者：
ROSEN, S
中科院分区：
文献类型：
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作者：
BREZIS, M;GREENFELD, Z;ROSEN, S
体外和体内研究了血管紧张素II （AII）对大鼠髓质缺氧损伤及肾功能的影响。在离体大鼠肾脏灌注液中加入人工合成AII可使灌注流量减少48。2毫升min-1 （.+-. se）至19 .+-。1 (P < 0.001)，没有改变肾小球滤过率（GFR），滤过率从1%提高到3% （P < 0.001）。aii扩展缺氧损伤髓质厚升肢（mTAL）从66。4%的小管到79 +-。3 （P < 0.05）与过滤分数相关（r = 0.8, P < 0.001）。吲哚美辛（10-4 mol l-1）的加入使髓质缺氧损伤进一步延长至89。2%的mTAL （P < 0.001）。在代谢笼中饲养未切除肾的大鼠，以0.1 ~ 0.8 μ连续输注AII。服用吲哚美辛（10 mg kg-1 day-1） 24 h。肌酐清除率从1.3±1下降。0.1 ml min-1至0.6 .+-。0.06 （p < 0.001）。形态学检查显示选择性坏死（12 .+-）。4%的小管)或管腔塌陷(63。8%)。坏死和塌陷与肌酐清除率呈负相关（r = -0.5, P < 0.001），后一相关性提示停止溶质输送可保护机体免受缺氧损伤。通过增加过滤分数和减少血流量。AII减少肾脏供氧，同时维持溶质再吸收的耗氧量。急性肾衰可通过增强髓质缺氧而诱发急性肾衰。
The effects of angiotensin II (AII) upon medullary hypoxic injury and kidney function were investigaed in vitro and in vivo. Synthetic AII added to perfusate of isolated rat kidneys reduced perfusion flow from 48 .+-. 2 ml min-1 (.+-.SE) to 19 .+-. 1 (P < 0.001) without altering glomerular filtration rate (GFR), raising filtration fraction from 1% to 3% (P < 0.001). AII-extended hypoxic injury to medullary thick ascending limbs (mTAL) from 66 .+-. 4% of tubules to 79 .+-. 3 (P < 0.05) in correlation with filtration fraction (r = 0.8, P < 0.001). Addition of indomethacin (10-4 mol l-1) further extended medullary hypoxic damage to 89 .+-. 2% of mTAL (P < 0.001). Uninephrectomized rats kept in metabolic cages were given AII by continuous infusion (0.1-0.8 .mu.g min-1) and indomethacin (10 mg kg-1 day-1) for 24 h. Creatinine clearance declined from 1.3 .+-. 0.1 ml min-1 to 0.6 .+-. 0.06 (P < 0.001). Morphological examination revealed either selective necrosis of mTAL (in 12 .+-. 4% of tubules) or luminal collapse (in 63 .+-. 8%). Both necrosis and collapse correlated inversely with creatinine clearance and with each other (r = -0.5, P < 0.001), and latter correlation suggesting protection from hypoxic injury by cessation of solute delivery. By increasing filtration fraction and decreasing blood flow. AII decreases renal oxygen supply while maintaining oxygen consumption for solute reabsorption. AII may predipose to acute renal failure by augmenting medullary hypoxia.