Bankir L, Fischer C, Fischer S, Jukkala K, Specht H C, Kriz W
INSERM Unité 90, Hôpital Necker, Paris, France.
Pflugers Arch. 1988 Jul;412(1-2):42-53. doi: 10.1007/BF00583730.
Previous experiments in Brattleboro rats with hereditary diabetes insipidus revealed that absence of ADH led to several alterations in kidney anatomy, which could be reversed by chronic ADH treatment. Present experiments were undertaken to determine if similar alterations were observable in normal Wistar rats when endogenous ADH level was varied by manipulating water intake or when exogenous ADH was infused. Water intake was increased by giving food with a high water content ad libitum and offering 5% glucose solution to drink (HWI rats), or decreased by reducing water intake to 1/3 of spontaneous intake (RWI rats). An additional group received chronic ADH infusion with Alzet osmotic minipumps (ADH rats). Results were compared to those obtained in control rats (CON) drinking ad libitum. RWI, CON, and ADH rats ate dry pellets ad libitum. After 6 weeks on these regimens kidneys were perfusion fixed and serial sections were cut for morphometric measurements by light microscopy. Results in the four groups showed that kidney weight relative to body weight was influenced by the operation of urinary concentrating mechanism, with HWI less than CON less than RWI less than ADH. The increase in kidney weight in rats with high urine concentration was not homogeneously distributed throughout the different kidney zones and the different nephron segments. The inner stripe of the outer medulla (IS) increased more in relative height and volume than other kidney zones and, within this zone, the volume of epithelium of thick ascending limb of Henle's loops (TAL) increased more than expected from the whole kidney weight increase. In outer stripe of outer medulla (OS) and in cortex (C), TAL hypertrophy was equal to or lower than expected from whole kidney weight increase. Collecting duct epithelium in C, OS, and IS increased in proportion to whole kidney weight. The MTAL hypertrophy in IS was due to an increase in size of preexisting cells, except in the ADH group where an increase in cell number was also observed. Internephron heterogeneity with regard to glomerular size was greater in RWI and ADH than in CON and HWI rats. The marked hypertrophy of the deep TAL in the IS of rats in which urine concentration was stimulated could be related to an increase in salt transport in this nephron segment, triggered both by a direct stimulation by ADH, and by an increased salt recycling. The elongation of the inner stripe provides a greater length for the operation of the countercurrent multiplier system responsible for building up of the osmotic pressure gradient in the medulla.(ABSTRACT TRUNCATED AT 400 WORDS)
先前针对遗传性尿崩症的布拉特洛维大鼠开展的实验表明，抗利尿激素（ADH）缺失会导致肾脏解剖结构出现多种改变，而长期进行ADH治疗可使其逆转。当前的实验旨在确定，在内源性ADH水平通过控制饮水量或注入外源性ADH而发生变化时，正常的Wistar大鼠是否会出现类似改变。通过随意投喂高含水量食物并提供5%葡萄糖溶液以供饮用，增加大鼠的饮水量（高饮水量大鼠，HWI）；或者将饮水量减少至自发饮水量的1/3，降低大鼠的饮水量（低饮水量大鼠，RWI）。另外一组大鼠通过Alzet渗透微型泵进行长期ADH注入（ADH大鼠）。将结果与自由饮水的对照大鼠（CON）所获结果进行比较。RWI、CON和ADH大鼠随意进食干颗粒饲料。在这些饲养方案实施6周后，对肾脏进行灌注固定，并制作连续切片，通过光学显微镜进行形态测量。四组实验结果显示，相对于体重而言，肾脏重量受尿液浓缩机制运作的影响，HWI组小于CON组，CON组小于RWI组，RWI组小于ADH组。尿液浓缩程度高的大鼠肾脏重量增加，并非均匀分布于不同的肾区和不同的肾单位节段。外髓质内带（IS）相对高度和体积的增加幅度大于其他肾区，在该区域内，亨氏袢厚升支（TAL）上皮细胞的体积增加幅度超过了基于整个肾脏重量增加所预期的幅度。在外髓质外带（OS）和皮质（C）中，TAL肥大程度等于或低于基于整个肾脏重量增加所预期的程度。C、OS和IS中的集合管上皮细胞随整个肾脏重量的增加而按比例增加。IS中MTAL的肥大是由于既有细胞体积增大所致，但ADH组除外，该组还观察到细胞数量增加。RWI和ADH大鼠肾小球大小的肾单位间异质性大于CON和HWI大鼠。在尿液浓缩受到刺激的大鼠中，IS内深层TAL的显著肥大可能与该肾单位节段盐转运增加有关，这是由ADH的直接刺激以及盐循环增加共同引发的。内带的延长为负责在髓质中建立渗透压梯度的逆流倍增系统的运作提供了更长的长度。（摘要截选至400词）
