BACKGROUND Preeclampsia poses a substantial clinical challenge, characterized by maternal hypertension, cardiac dysfunction, and persistent cardiovascular risks for both the mother and offspring. Despite the known roles of the estrogen receptor (GPER [G protein-coupled estrogen receptor]) in placental development, its impact on cardiovascular aspects within a preeclampsia animal model remains unexplored. We propose that G-1, a GPER agonist, could have the potential to regulate not only hypertension but also cardiac dysfunction in rats with preeclampsia. METHODS To explore the influence of G-1 on preeclampsia, we used the reduced uterine perfusion pressure (RUPP) model. RUPP rats were administered either G-1 (100 µg/kg per day) or hydralazine (25 mg/kg per day). We conducted echocardiography to probe the intricate cardiac effects of G-1. RESULTS The RUPP rat model revealed signs of hypertension and cardiac dysfunction and alterations in gene and protein expression within placental and heart tissues. G-1 treatment reduced blood pressure and reversed cardiac dysfunction in rats with preeclampsia. In contrast, administration of the vasodilator hydralazine reduced blood pressure without an improvement in cardiac function. In addition, while G-1 treatment restored the levels of sFLT-1 (soluble fms-like tyrosine kinase-1) in RUPP rats, hydralazine did not normalize this antiangiogenic factor. CONCLUSIONS The therapeutic intervention of G-1 significantly mitigated the cardiovascular dysfunction observed in the RUPP rat model of preeclampsia. This discovery underscores the broader significance of understanding GPER's role in the context of preeclampsia-related cardiovascular complications.

中文翻译：

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GPER 刺激减轻子痫前期大鼠模型中的功能障碍。


背景 子痫前期构成了巨大的临床挑战，其特征是母亲和后代的母体高血压、心功能不全和持续的心血管风险。尽管雌激素受体 （GPER [G 蛋白偶联雌激素受体]）在胎盘发育中的作用已知，但其对子痫前期动物模型中心血管方面的影响仍未得到探索。我们提出 G-1 是一种 GPER 激动剂，不仅可以调节高血压，还可以调节子痫前期大鼠的心功能不全。方法 为了探讨 G-1 对子痫前期的影响，我们使用了降低子宫灌注压 （RUPP） 模型。RUPP 大鼠给予 G-1 （100 μg/kg /天） 或肼屈嗪 （25 mg/kg /天）。我们进行了超声心动图以探索 G-1 对心脏的复杂影响。结果 RUPP 大鼠模型揭示了高血压和心功能不全的迹象以及胎盘和心脏组织内基因和蛋白质表达的改变。G-1 治疗降低了子痫前期大鼠的血压并逆转了心功能障碍。相比之下，血管扩张剂肼屈嗪的给药降低了血压，而心脏功能没有改善。此外，虽然 G-1 治疗恢复了 RUPP 大鼠 sFLT-1 （可溶性 fms 样酪氨酸激酶-1） 的水平，但肼屈嗪并未使这种抗血管生成因子正常化。结论 G-1 的治疗干预显著减轻了在 RUPP 大鼠子痫前期模型中观察到的心血管功能障碍。这一发现强调了了解 GPER 在子痫前期相关心血管并发症中的作用的更广泛意义。