Early polyuria and urinary concentrating defect in potassium deprivation
Early polyuria and urinary concentrating defect in potassium deprivation
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DOI：
10.1152/ajprenal.2000.279.4.f655
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发表时间：
2000-10-01
影响因子：
4.2
通讯作者：
Soleimani, M
中科院分区：
文献类型：
--
作者：
Amlal, H;Krane, CM;Soleimani, M
肾源性尿崩症的发病时间及其与K+剥夺（KD）中水通道蛋白-2 （AQP2）表达的关系尚不清楚。各组大鼠分别饲喂无K+日粮，分别于12 h、1、2、3、6、21 d处死。血清K+浓度仅在无K+饮食3天后下降，而在无K+饮食3天后没有下降。然而，尿渗透压早在KD后12 h就下降了（1061 +/- 26 vs. 1487 +/- 102 mosmol/kgH，对照组，P < 0.01）。24 h时进一步下降（KD为858 +/- 162 mosmol/kgH(2)O, P < 0.004）， 21 d时保持在较低水平（436 +/- 58 mosmol/kgH(2)O，与基线相比P < 0.0001）。饮水量在12 h时下降（P < 0.002），在24 h时增加（P < 0.05），并在KD 21 d时保持较高水平。24 h时尿量增加（8 +/- 2 ~ 15 +/- 2 ml/24 h, P < 0.05）， 21 d时尿量继续升高。免疫印迹分析显示，体外髓质AQP2蛋白丰度在12 h时保持不变（P < 0.05），在24 h时下降（相似于44%，P < 0.001），在KD后21 d时保持抑制（相似于52%，P < 0.03）。内髓质AQP2蛋白的丰度在KD作用12和24 h时保持不变。然而，皮质AQP2蛋白丰度在KD作用12 h时下降（相似于47%，P < 0.01），在KD作用24 h时保持抑制（相似于77%，P < 0.001）。Northern blot分析显示，AQP2 mRNA在大鼠皮层（P < 0.02）和外髓质（P < 0.01）的KD均在12 h时降低，此后仍保持抑制状态。总之，KD的尿浓缩缺陷是一个早期事件，早于低钾血症的发生。这些研究进一步表明，KD的早期尿浓缩缺陷（12小时后但24小时前）主要是由于皮质AQP2的抑制，而尿浓缩缺陷的晚发（24小时后）也与髓质AQP2的下调有关。
The time course of the onset of nephrogenic diabetes insipidus and its relationship to aquaporin-2 (AQP2) expression in K+ deprivation (KD) remains unknown. Rats were fed a K+-free diet and killed after 12 h, 1, 2, 3, 6, or 21 days. Serum K+ concentration was decreased only after, but not before, 3 days of a K+-free diet. Urine osmolality, however, decreased as early as 12 h of KD (1,061 +/- 26 vs. 1,487 +/- 102 mosmol/kgH(2)O in control, P < 0.01). It decreased further at 24 h (to 858 +/- 162 mosmol/ kgH(2)O in KD, P < 0.004) and remained low at 21 days of KD (436 +/- 58 mosmol/kgH(2)O, P < 0.0001 compared with baseline). Water intake decreased at 12 h (P < 0.002) but increased at 24 h (P < 0.05) and remained elevated at 21 days of KD. Urine volume increased at 24 h of KD (8 +/- 2 to 15 +/- 2 ml/24 h, P < 0.05) and remained elevated at 21 days. Immunoblot analysis demonstrated that AQP2 protein abundance in the outer medulla remained unchanged at 12 h (P > 0.05), decreased at 24 h (similar to 44%, P < 0.001), and remained suppressed (similar to 52%, P < 0.03) at 21 days of KD. In the inner medulla the AQP2 protein abundance remained unchanged at both 12 and 24 h of KD. AQP2 protein abundance in the cortex, however, decreased at 12 h (similar to 47%, P < 0.01) and remained suppressed at 24 h (similar to 77%, P < 0.001) of KD. Northern blot analysis showed that AQP2 mRNA decreased as early as 12 h of KD in both cortex (P < 0.02) and outer medulla (P < 0.01) and remained suppressed afterward. In conclusion, the urinary concentrating defect in KD is an early event and precedes the onset of hypokalemia. These studies further suggest that the very early urinary concentrating defect in KD (after 12 but before 24 h) results primarily from the suppression of cortical AQP2, whereas the later onset of a urinary concentrating defect (after 24 h) also involves a downregulation of medullary AQP2.