Activation of G protein-coupled estrogen receptor 1 ameliorates proximal tubular injury and proteinuria in Dahl salt-sensitive female rats
Activation of G protein-coupled estrogen receptor 1 ameliorates proximal tubular injury and proteinuria in Dahl salt-sensitive female rats
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DOI：
10.1152/ajpregu.00267.2020
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发表时间：
2021-03-01
影响因子：
2.8
通讯作者：
De Miguel, Carmen
中科院分区：
文献类型：
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作者：
Gohar, Eman Y.;Almutlaq, Rawan N.;De Miguel, Carmen
最近的证据表明，G蛋白偶联雌激素受体1（GPER 1）在维持女性心血管和肾脏健康中起着至关重要的作用。目前的研究测试了GPER 1激活是否改善了喂食高盐（HS）饮食的雌性Dahl盐敏感（SS）大鼠的高血压和肾损伤。成年雌性大鼠植入遥测发射机监测血压和渗透压微泵释放G1（选择性GPER 1激动剂，400？g/kg/天ip）或媒介物。泵植入后两周，大鼠从正常盐（NS）饮食（0.4%NaCl）转换为匹配的HS饮食（4.0%NaCl）2周。在两个饮食期间收集24小时尿样，并评估肾损伤的尿标记物。在2周HS饮食期后进行肾损伤的组织学评估。与NS饮食期间的值相比，24小时平均动脉压显着增加响应HS，达到相似的值，在溶剂处理和G1处理的大鼠。HS还显著增加了溶剂处理大鼠的蛋白质、白蛋白、nephrin（足细胞损伤标记物）和KIM-1（近端小管损伤标记物）的尿排泄。重要的是，G1治疗预防HS诱导的蛋白尿、白蛋白尿和KIM-1排泄增加，但不能预防肾蛋白尿。组织学分析显示，HS诱导的肾小球损伤组间无差异。然而，G1处理保留了HS喂养大鼠近端小管刷状缘的完整性。总的来说，我们的数据表明，GPER 1激活保护HS诱导的蛋白尿和白蛋白尿在雌性Dahl SS大鼠通过保持近端小管刷状缘的完整性，在血压独立的方式。
Recent evidence indicates a crucial role for G protein-coupled estrogen receptor 1 (GPER1) in the maintenance of cardiovascular and kidney health in females. The current study tested whether GPER1 activation ameliorates hypertension and kidney damage in female Dahl salt-sensitive (SS) rats fed a high-salt (HS) diet. Adult female rats were implanted with telemetry transmitters for monitoring blood pressure and osmotic minipumps releasing G1 (selective GPER1 agonist, 400 ?g/kg/day ip) or vehicle. Two weeks after pump implantation, rats were shifted from a normal-salt (NS) diet (0.4% NaCl) to a matched HS diet (4.0% NaCl) for 2 wk. Twenty-four hour urine samples were collected during both diet periods and urinary markers of kidney injury were assessed. Histological assessment of kidney injury was conducted after the 2-wk HS diet period. Compared with values during the NS diet, 24-h mean arterial pressure markedly increased in response to HS, reaching similar values in vehicle-treated and G1-treated rats. HS also significantly increased urinary excretion of protein, albumin, nephrin (podocyte damage marker), and KIM-1 (proximal tubule injury marker) in vehicle-treated rats. Importantly, G1 treatment prevented the HS-induced proteinuria, albuminuria, and increase in KIM-1 excretion but not nephrinuria. Histological analysis revealed that HS-induced glomerular damage did not differ between groups. However, G1 treatment preserved proximal tubule brush-border integrity in HS-fed rats. Collectively, our data suggest that GPER1 activation protects against HS-induced proteinuria and albuminuria in female Dahl SS rats by preserving proximal tubule brush-border integrity in a blood pressure-independent manner.