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 μg/kg/day, intraperitoneal) or vehicle. Two weeks after pump implantation, rats were shifted from a normal salt diet (NS, 0.4% NaCl) to a matched HS diet (4.0% NaCl) for 2 weeks. 24-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-week HS diet period. Compared with values during the NS diet, 24-hour 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.

中文翻译：

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激活 G 蛋白偶联雌激素受体 1 可改善 Dahl 盐敏感性雌性大鼠的近端肾小管损伤和蛋白尿

最近的证据表明 G 蛋白偶联雌激素受体 1 (GPER1) 在维持女性心血管和肾脏健康方面发挥着至关重要的作用。目前的研究测试了 GPER1 激活是否可以改善喂食高盐 (HS) 饮食的雌性 Dahl 盐敏感 (SS) 大鼠的高血压和肾损伤。成年雌性大鼠被植入遥测发射器以监测血压和释放 G1（选择性 GPER1 激动剂，400 μg/kg/天，腹膜内）或载体的渗透性微型泵。泵植入两周后，大鼠从正常盐饮食（NS，0.4% NaCl）转变为匹配的 HS 饮食（4.0% NaCl），持续 2 周。在两个饮食期间收集 24 小时尿液样本，并评估肾损伤的尿液标志物。在 2 周的 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 小时平均动脉压响应 HS 显着增加，在载体处理和 G1 处理的大鼠中达到相似的值。在载体处理的大鼠中，HS 还显着增加了蛋白质、白蛋白、nephrin（足细胞损伤标志物）和 KIM-1（近端小管损伤标志物）的尿排泄。重要的是，G1 治疗可防止 HS 诱导的蛋白尿、白蛋白尿和 KIM-1 排泄增加，但不能防止肾尿。组织学分析显示，HS 诱导的肾小球损伤在各组之间没有差异。然而，G1 治疗保留了 HS 喂养大鼠的近端小管刷状缘完整性。集体，