Adaptation of the rat kidney to altered water intake and urine concentration

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Abstract
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<CON<RWI<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 hyperthrophy 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. These observations show that the mammalian kidney is able to adapt to chronic alterations in water intake and urine concentration status.