Restoration of Connexin 40 (Cx40) in Renin-Producing Cells Reduces the Hypertension of Cx40 Null Mice
Restoration of Connexin 40 (Cx40) in Renin-Producing Cells Reduces the Hypertension of Cx40 Null Mice
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DOI：
10.1161/hypertensionaha.113.02976
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发表时间：
2014-06-01
期刊：
影响因子：
8.3
通讯作者：
Haefliger, Jacques-Antoine
中科院分区：
文献类型：
--
作者：
Le Gal, Loic;Alonso, Florian;Haefliger, Jacques-Antoine
连接蛋白40（Cx40）由肾脏的产生肾素的细胞（RSC）和血管的内皮细胞表达。Cx40基因敲除小鼠（Cx40（-/-））的特征在于大量增加的肾素合成和分泌，这导致慢性高血压，并且还显示由于eNOS水平降低和一氧化氮产生而改变的主动脉内皮依赖性舒张。为了区分Cx40在肾素分泌和血管信号传导中的作用，我们将Cx40靶向Cx40缺失小鼠的RSC或内皮细胞。与Cx40（-/-）对照组相比，在RSC中表达Cx40的动物血压较低，并且具有降低的肾素水平，在传入小动脉壁外仍有大量RSC。相比之下，在内皮细胞中表达Cx40的小鼠与Cx40（-/-）小鼠一样高血压，尽管Cx 37和eNOS的控制水平。我们的数据表明，血压的改善是通过恢复Cx40在RSC中的表达，但不是在内皮细胞，强调突出的作用，肾素在小鼠高血压与损失的Cx40。
Connexin 40 (Cx40) is expressed by the renin-producing cells (RSCs) of the kidneys and the endothelial cells of blood vessels. Cx40 null mice (Cx40(-/-)) feature a much increased renin synthesis and secretion, which results in chronic hypertension, and also display an altered endothelium-dependent relaxation of the aorta because of reduced eNOS levels and nitric oxide production. To discriminate the effect of Cx40 in renin secretion and vascular signaling, we targeted Cx40 to either the RSCs or the endothelial cells of Cx40 null mice. When compared with Cx40(-/-) controls, the animals expressing Cx40 in RSCs were less hypertensive and featured reduced renin levels, still numerous RSCs outside the wall of the afferent arterioles. In contrast, mice expressing Cx40 in the endothelial cells were as hypertensive as Cx40(-/-) mice, in spite of control levels of Cx37 and eNOS. Our data show that blood pressure is improved by restoration of Cx40 expression in RSCs but not in endothelial cells, stressing the prominent role of renin in the mouse hypertension linked to loss of Cx40.