Stimulation of Epithelial Sodium Channels in Endothelial Cells by Bone Morphogenetic Protein-4 Contributes to Salt-Sensitive Hypertension in Rats.
Stimulation of Epithelial Sodium Channels in Endothelial Cells by Bone Morphogenetic Protein-4 Contributes to Salt-Sensitive Hypertension in Rats.
复制标题
骨形态发生蛋白 4 刺激内皮细胞中的上皮钠通道导致大鼠盐敏感性高血压
DOI：
10.1155/2020/3921897
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发表时间：
2020
影响因子：
--
通讯作者：
Zhang ZR
中科院分区：
文献类型：
--
作者：
Yang X;Niu N;Liang C;Wu MM;Tang LL;Wang QS;Lou J;Song BL;Zheng WW;Ma HP;Zhang ZR
先前的研究表明，高盐通过增加钠流入引起内皮功能障碍，从而导致动脉僵硬。我们使用独特的劈开动脉技术，结合蛋白质生物化学和体外血管张力测量来测试骨形态发生蛋白 4 (BMP4) 通过刺激内皮细胞中的上皮钠通道 (ENaC) 介导高盐诱导的血管松弛丧失的假设。数据显示，高盐摄入量增加了内皮细胞和血清中的 BMP4，并且外源 BMP4 刺激了内皮细胞中的 ENaC。数据还表明，刺激是由 p38 丝裂原激活蛋白激酶 (p38 MAPK) 以及血清和糖皮质激素调节激酶 1 (Sgk1)/神经前体细胞表达的发育下调基因 4-2 (Nedd4-2) (Sgk1/Nedd4-2) 介导的。此外，BMP4 以苯扎米尔敏感的方式减少肠系膜动脉松弛。这些结果表明，高盐摄入会刺激内皮细胞表达和释放 BMP4，并且释放的 BMP4 通过刺激内皮细胞中的 ENaC 来减少动脉松弛。因此，BMP4刺激内皮细胞中的ENaC可能作为参与盐敏感性（SS）高血压复杂机制的另一途径。
Previous studies have shown that high salt induces artery stiffness by causing endothelial dysfunction via increased sodium influx. We used our unique split-open artery technique combined with protein biochemistry and in vitro measurement of vascular tone to test a hypothesis that bone morphogenetic protein 4 (BMP4) mediates high salt-induced loss of vascular relaxation by stimulating the epithelial sodium channel (ENaC) in endothelial cells. The data show that high salt intake increased BMP4 both in endothelial cells and in the serum and that exogenous BMP4 stimulated ENaC in endothelial cells. The data also show that the stimulation is mediated by p38 mitogen-activated protein kinases (p38 MAPK) and serum and glucocorticoid-regulated kinase 1 (Sgk1)/neural precursor cell expressed developmentally downregulated gene 4-2 (Nedd4-2) (Sgk1/Nedd4-2). Furthermore, BMP4 decreased mesenteric artery relaxation in a benzamil-sensitive manner. These results suggest that high salt intake stimulates endothelial cells to express and release BMP4 and that the released BMP4 reduces artery relaxation by stimulating ENaC in endothelial cells. Therefore, stimulation of ENaC in endothelial cells by BMP4 may serve as another pathway to participate in the complex mechanism of salt-sensitive (SS) hypertension.