Brezis M, Greenfeld Z, Shina A, Rosen S
Department of Medicine, Hadassah University Hospital, Jerusalem, Israel.
Eur J Clin Invest. 1990 Apr;20(2):199-207. doi: 10.1111/j.1365-2362.1990.tb02269.x.
The effects of angiotensin II (AII) upon medullary hypoxic injury and kidney function were investigated 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 less than 0.001) without altering glomerular filtration rate (GFR), raising filtration fraction from 1% to 3% (P less than 0.001). AII-extended hypoxic injury to medullary thick ascending limbs (mTAL) from 66 +/- 4% of tubules to 79 +/- 3 (P less than 0.05) in correlation with filtration fraction (r = 0.8, P less than 0.001). Addition of indomethacin (10(-4) mol l-1) further extended medullary hypoxic damage to 89 +/- 2% of mTAL (P less than 0.001). Uninephrectomized rats kept in metabolic cages were given AII by continuous infusion (0.1-0.8 microgram 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 less than 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 less than 0.001), the 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 predispose to acute renal failure by augmenting medullary hypoxia.
在体外和体内研究了血管紧张素II（AII）对髓质缺氧损伤和肾功能的影响。添加到离体大鼠肾脏灌注液中的合成AII使灌注流量从48±2 ml/min（±标准误）降至19±1（P<0.001），而不改变肾小球滤过率（GFR），滤过分数从1%提高到3%（P<0.001）。AII使髓质厚升支（mTAL）的缺氧损伤从66±4%的肾小管扩展至79±3（P<0.05），与滤过分数相关（r = 0.8，P<0.001）。添加吲哚美辛（10⁻⁴ mol/L）进一步将髓质缺氧损伤扩展至89±2%的mTAL（P<0.001）。将单侧肾切除的大鼠置于代谢笼中，通过持续输注给予AII（0.1 - 0.8 μg/min）和吲哚美辛（10 mg/kg·天），持续24小时。肌酐清除率从1.3±0.1 ml/min降至0.6±0.06（P<0.001）。形态学检查显示mTAL要么发生选择性坏死（占肾小管的12±4%），要么发生管腔塌陷（占63±8%）。坏死和塌陷均与肌酐清除率呈负相关且二者之间也呈负相关（r = -0.5，P<0.001），后一种相关性表明溶质输送停止可保护免受缺氧损伤。通过增加滤过分数和减少血流，AII在维持溶质重吸收氧消耗的同时减少了肾脏的氧供应。AII可能通过加剧髓质缺氧而导致急性肾衰竭。
