Upregulation of aquaporin 2 water channel expression in pregnant rats.
Upregulation of aquaporin 2 water channel expression in pregnant rats.
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DOI：
10.1172/jci649
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发表时间：
1998-03
期刊：
影响因子：
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通讯作者：
M. Ohara;P. Martin;Ding-li Xu;J. John;T. Pattison;J. K. Kim;R. Schrier
中科院分区：
文献类型：
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作者：
M. Ohara;P. Martin;Ding-li Xu;J. John;T. Pattison;J. K. Kim;R. Schrier
水潴留是妊娠的特征，但水代谢改变的机制尚未阐明。水通道蛋白2 （aquaporin 2, AQP2）在肾脏水分调节中起关键作用，我们推测AQP2的表达可能在妊娠期间发生改变。以Sprague-Dawley雌性大鼠妊娠第7天（P7）、第14天（P14）、第20天（P20）为实验动物，检测AQP2在乳头中的表达。未怀孕（NP）的幼崽作为对照。妊娠第7天，妊娠大鼠血浆渗透压明显降低（P7 283.8+/-1.82, P14 284.3+/-1.64, P < 0.001, P20 282）。4+/-1.32, P < 0.0001，与NP 291.8+/-1.06 mosmol/kgH2O相比)。妊娠大鼠血浆抗利尿激素浓度与未妊娠大鼠无显著差异（NP 1.03+/-0.14, P7 1.11+/-0.21, P14 1.15+/-0.21, P20 1.36+/-0.24 pg/ml， NS）。妊娠早期AQP2 mRNA升高：AQP2/ β肌动蛋白：P7 196+/-17.9, P14 200+/-6.8, P20 208+/-15.5%, P < 0.005，与NP（100+/-11.1%）比较。AQP2蛋白：P7 269+/-10.0, P14 251+/-12.0, P < 0.0001, P20 250+/-13.6%, P < 0.001, P < NP（100+/-12.5%）。然后研究V2抗利尿激素受体拮抗剂OPC-31260的作用。OPC-31260显著抑制了P14大鼠AQP2 mRNA的表达（OPC-31260组AQP2/ β肌动蛋白：P14组为39.6+/-1.7%,P < 0.001，对照组为P14组），并降低至与NP大鼠OPC-31260组相同的表达水平。对AQP2蛋白的分析也发现了类似的结果。OPC-31260对P14大鼠血浆渗透压降低无明显影响。本研究结果表明，AQP2的上调通过V2受体介导的作用参与妊娠期水分潴留。除抗利尿激素外，其他因素也可能参与这种上调。
Water retention is characteristic of pregnancy but the mechanism(s) of the altered water metabolism has yet to be elucidated. The collecting duct water channel, aquaporin 2 (AQP2), plays a pivotal role in the renal water regulation, and we hypothesized that AQP2 expression could be modified during pregnancy. Sprague-Dawley female rats were studied on days 7 (P7), 14 (P14), and 20 (P20) of pregnancy, and expression of AQP2 in papillae was examined. Nonpregnant (NP) littermates were used as controls. Plasma osmolalities were significantly lower in pregnant rats by day 7 of gestation (P7 283.8+/-1.82, P14 284.3+/-1.64, P < 0.001, P20 282. 4+/-1.32, P < 0.0001, vs. NP 291.8+/-1.06 mosmol/kgH2O). However, plasma vasopressin concentrations in pregnant rats were not significantly different than in nonpregnant rats (NP 1.03+/-0.14, P7 1.11+/-0.21, P14 1.15+/-0.21, P20 1.36+/-0.24 pg/ml, NS). The mRNA of AQP2 was increased early during pregnancy: AQP2/beta actin: P7 196+/-17.9, P14 200+/-6.8, and P20 208+/-15.5%, P < 0.005 vs. NP (100+/-11.1%). AQP2 protein was also increased during pregnancy: AQP2 protein: P7 269+/-10.0, P14 251+/-12.0, P < 0.0001, and P20 250+/-13.6%, P < 0.001 vs. NP (100+/-12.5%). The effect of V2 vasopressin receptor antagonist, OPC-31260, was then investigated. AQP2 mRNA was suppressed significantly by OPC-31260 administration to P14 rats (AQP2/beta actin: P14 with OPC-31260 39.6+/-1.7%, P < 0.001 vs. P14 with vehicle) and was decreased to the same level of expression as NP rats receiving OPC-31260. Similar findings were found with the analysis of AQP2 protein. The decreased plasma osmolality of P14 rats was not modified by OPC-31260. The results of the study indicate that upregulation of AQP2 contributes to the water retention in pregnancy through a V2 receptor-mediated effect. In addition to vasopressin, other factors may be involved in this upregulation.