(Pro)renin receptor contributes to pregnancy-induced sodium-water retention in rats via activation of intrarenal RAAS and α-ENaC
(Pro)renin receptor contributes to pregnancy-induced sodium-water retention in rats via activation of intrarenal RAAS and α-ENaC
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DOI：
10.1152/ajprenal.00411.2018
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发表时间：
2019-03-01
影响因子：
4.2
通讯作者：
Yang, Tianxin
中科院分区：
文献类型：
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作者：
Fu, Ziwei;Hu, Jiajia;Yang, Tianxin
肾素受体（PRR）是肾素-血管紧张素-醛固酮系统（RAAS）的一个新组成部分，调节肾素活性。本研究的目的是测试肾脏PRR和肾内RAAS在妊娠后期生理状态中的潜在作用。在阴道涂片观察到精子后19-21天对妊娠晚期的Sprague-Dawley大鼠进行研究。实验采用年龄匹配的初孕大鼠和孕晚期大鼠，分别给予特异性PRR抑制剂PRO20 （700 μ g.kg(-1)）处理。天（-1）sc，连续14天，每8小时3次/天)或车辆。免疫印迹法检测RAAS的PRR、肾素、血管紧张素II和醛固酮水平。qRT-PCR或ELISA。进一步分析肾上皮钠通道（ENaC）表达、钠-水潴留和血浆容量。我们首先提出了妊娠晚期大鼠肾内RAAS激活的证据，包括尿肾素活性、活性肾素和总肾素含量以及促肾素含量的增加。血管紧张素II和醛固酮排泄。同时肾脏PRR表达和尿可溶性PRR排泄增加。功能证据表明，PRR拮抗剂PRO20能有效抑制妊娠晚期大鼠肾内RAAS指标。此外，我们的研究结果显示，妊娠后期肾脏α - enac表达、钠水潴留和血浆体积升高，均被PRO20减弱。综上所述，本研究考察了妊娠晚期大鼠肾内钠水潴留和血浆容量扩张的机制，并确定了PRR在调节肾内RAAS和α - enac以及与妊娠相关的钠和液体潴留中的新作用。
The (pro)renin receptor (PRR) is a new component of the renin-angiotensin-aldosterone system (RAAS) and regulates renin activity. The objective of the present study was to test potential roles of the renal PRR and intrarenal RAAS in the physiological status of late pregnancy. Late pregnant Sprague-Dawley rats were studied 19-21 days after sperm was observed in vaginal smears. Experiments were performed using age-matched virgin rats and late pregnant rats treated with the specific PRR inhibitor PRO20 (700 mu g.kg(-1).day(-1) sc for 14 days, 3 times/day for every 8 h) or vehicle. The indices of RAAS, including PRR, renin, angiotensin II, and aldosterone levels, were examined by immunoblotting. qRT-PCR, or ELISA. Further analyses of renal epithelial sodium channel (ENaC) expression, sodium-water retention, and plasma volume were performed. We first present evidence for the activation of intrarenal RAAS in late pregnant rats, including increases in urinary renin activity, active and total renin content, and prorenin content. angiotensin II and aldosterone excretion. in parallel with increased renal PRR expression and urinary soluble PRR excretion. Functional evidence demonstrated that PRR antagonism with PRO20 effectively suppressed the indices of intrarenal RAAS in late pregnant rats. In addition, our results revealed that renal alpha-ENaC expression, sodium-water retention, and plasma volume were elevated during late pregnancy, which were all attenuated by PRO20. In summary, the present study examined the renal mechanism of sodium-water retention and plasma volume expansion in late pregnant rats and identified a novel role of PRR in regulation of intrarenal RAAS and alpha-ENaC and thus sodium and fluid retention associated with pregnancy.