Mills Natalie J, Sharma Kaustubh, Huang Katie, Teruyama Ryoichi
Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana.
Physiol Rep. 2018 Aug;6(16):e13838. doi: 10.14814/phy2.13838.
All three epithelial Na channel (ENaC) subunits (α, β, and γ) and the mineralocorticoid receptor (MR), a known regulator of ENaC, are located in vasopressin (VP) synthesizing magnocellular neurons in the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei. Our previous study showed that ENaC mediates a Na leak current that affects the steady-state membrane potential of VP neurons. This study was conducted in Dahl salt-sensitive (Dahl-SS) rats to determine if any abnormal responses in the expression of ENaC subunits and MR occur in the hypothalamus and kidney in response to a high dietary salt intake. After 21 days of high salt consumption, Dahl-SS rat resulted in a significant increase in γENaC expression and exhibited proteolytic cleavage of this subunit compared to Sprague-Dawley (SD) rats. Additionally, Dahl-SS rats had dense somato-dendritic γENaC immunoreactivity in VP neurons, which was absent in SD rats. In contrast, SD rats fed a high salt diet had significantly decreased αENaC subunit expression in the kidney and MR expression in the hypothalamus. Plasma osmolality measured daily for 22 days demonstrated that Dahl-SS rats fed a high salt diet had a steady increase in plasma osmolality, whereas SD rats had an initial increase that decreased to baseline levels. Findings from this study demonstrate that Dahl-SS rats lack a compensatory mechanism to down regulate ENaC during high dietary salt consumption, which may contribute to the development of hypertension.
所有三种上皮钠通道（ENaC）亚基（α、β和γ）以及盐皮质激素受体（MR，一种已知的ENaC调节因子）都位于下丘脑视上核（SON）和室旁核（PVN）中合成血管加压素（VP）的大细胞神经元中。我们之前的研究表明，ENaC介导一种钠泄漏电流，该电流会影响VP神经元的稳态膜电位。本研究以 Dahl 盐敏感（Dahl-SS）大鼠为对象，以确定在高盐饮食摄入情况下，下丘脑和肾脏中ENaC亚基和MR的表达是否会出现任何异常反应。在高盐饮食21天后，与Sprague-Dawley（SD）大鼠相比，Dahl-SS大鼠的γENaC表达显著增加，并且该亚基出现了蛋白水解切割。此外，Dahl-SS大鼠的VP神经元中存在密集的体树突γENaC免疫反应性，而SD大鼠中则没有。相比之下，喂食高盐饮食的SD大鼠肾脏中的αENaC亚基表达和下丘脑中的MR表达显著降低。连续22天每日测量血浆渗透压表明，喂食高盐饮食的Dahl-SS大鼠血浆渗透压稳步升高，而SD大鼠则是先升高，随后降至基线水平。本研究结果表明，Dahl-SS大鼠在高盐饮食期间缺乏下调ENaC的代偿机制，这可能导致高血压的发生。
