Connexin40 regulates renin production and blood pressure
Connexin40 regulates renin production and blood pressure
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DOI：
10.1038/sj.ki.5002423
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发表时间：
2007-10-01
影响因子：
19.6
通讯作者：
Haefliger, J-A
中科院分区：
文献类型：
--
作者：
Krattinger, N.;Capponi, A.;Haefliger, J-A
肾素分泌通过肾小球旁器官的各个细胞之间的协调信号传导进行调节。肾素分泌细胞 (RSC) 在血压控制中发挥着重要作用，它们通过含有 Connexin40 (Cx40) 的通道相互偶联并与内皮细胞偶联。在这项研究中，我们发现 Cx40 敲除 (Cx40-/-) 小鼠（而非其杂合同窝小鼠）由于 RSC、肾素生物合成和血浆肾素数量增加而患有高血压。使用血管紧张素 II 受体 AT1 拮抗剂坎地沙坦或血管紧张素 II 转换酶抑制剂雷米普利治疗可将 Cx40 -/- 小鼠的血压降低至与野生型 (WT) 小鼠相同的水平。基因敲除小鼠的血压升高不受剪断一根肾动脉（2K1C，肾依赖性高血压模型）或高盐饮食后的影响。然而，在这些条件下，Cx40 -/- 小鼠表现出肾素产生和释放的改变。基因敲除小鼠中，剪断肾脏和未剪断肾脏之间的肾素 mRNA 比率低于 WT 2K1C 小鼠。这表明对血压变化的反应发生了改变。 Cx40 -/- 小鼠的 RSC 中 Cx43 或 Cx37 的水平没有代偿性增加。我们的数据显示肾素分泌依赖于Cx40，表明Cx40 -/- 小鼠可能是肾素依赖性高血压的遗传模型。
Renin secretion is regulated by coordinated signaling between the various cells of the juxtaglomerular apparatus. The renin-secreting cells (RSC), which play a major role in the control of blood pressure, are coupled to each other and to endothelial cells by Connexin40 (Cx40)-containing channels. In this study, we show that Cx40 knockout (Cx40-/-) mice, but not their heterozygous littermates, are hypertensive due to the increase in the number of RSC, renin biosynthesis, and plasma renin. Treatment with the angiotensin II receptor AT1 antagonist candesartan or the angiotensin II-converting enzyme inhibitor ramipril reduced the blood pressure of the Cx40 -/- mice to the same levels seen in wild-type (WT) mice. The elevated blood pressure of the knockout mice was not affected by clipping one renal artery (2K1C, renindependent model of hypertension) or after a high salt diet. Under these conditions, however, Cx40 -/- mice showed an altered production and release of renin. The renin mRNA ratio between the clipped and the non-clipped kidney was lower in the knockout than in the WT 2K1C mice. This indicates that the response to a change in blood pressure was altered. The RSC of the Cx40 -/- mice did not have a compensatory increase in the levels of either Cx43 or Cx37. Our data show that renin secretion is dependent on Cx40 and suggest the Cx40 -/- mice may be a genetic model of renin-dependent hypertension.