Endothelial Sodium Channels Trigger Endothelial Salt Sensitivity With Aging
Endothelial Sodium Channels Trigger Endothelial Salt Sensitivity With Aging
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DOI：
10.1161/hypertensionaha.114.03348
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发表时间：
2014-08-01
期刊：
影响因子：
8.3
通讯作者：
Kliche, Katrin
中科院分区：
文献类型：
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作者：
Paar, Moritz;Pavenstaedt, Hermann;Kliche, Katrin
上皮钠通道也在血管内皮中表达（内皮钠通道[EnNaC]）。根据环境钠浓度，EnNaC与内皮细胞皮质的机械硬化有关，导致内皮功能障碍。由于盐敏感性和内皮功能障碍的发生率随着年龄的增长而增加，我们研究了衰老小鼠中EnNaC的丰度。为了评估EnNaC功能和内皮盐敏感性，在环境钠变化时测量硬度。实验用生理浓度0.45 nmol/L的醛固酮饲养幼龄（3月龄）和老龄（15月龄）C57BL/6J野生型小鼠主动脉。螺内酯（10 nmol/L）和阿米洛利（1 mol/L）分别用于醛固酮拮抗和EnNaC阻断。免疫荧光染色定量内皮细胞表面EnNaC。当环境钠从135 mmol/L增加到150 mmol/L时，用原子力显微镜监测皮质刚度。在老年小鼠离体主动脉中，内皮细胞的EnNaC含量明显高于年轻小鼠（+23%）。同时，皮质刚度增加（+8.5%）。急性应用高钠导致两组小鼠的僵硬度立即升高，但老年小鼠的内皮细胞明显升高（+18%对+26%）。在所有条件下，螺内酯和阿米洛利降低EnNaC丰度并防止内皮硬化。我们认为EnNaC介导了衰老过程中内皮细胞对盐的敏感性。这一机制可能促进了年龄相关心血管疾病的发展，并建议在老年人中特别使用螺内酯和阿米洛利。
The epithelial sodium channel is also expressed in vascular endothelium (endothelial sodium channel [EnNaC]). Depending on ambient sodium concentration, EnNaC is associated with mechanical stiffening of the endothelial cell cortex, leading to endothelial dysfunction. Because the incidence of both salt sensitivity and endothelial dysfunction increases with age, we investigated the abundance of EnNaC in aging mice. To assess EnNaC functionality and endothelial salt sensitivity, stiffness was measured while ambient sodium was varied. Aortae of young (3 months) and old (15 months) C57BL/6J wild-type mice were kept ex vivo on a physiological concentration of aldosterone (0.45 nmol/L). Spironolactone (10 nmol/L) and amiloride (1 mol/L) were applied for aldosterone antagonism and EnNaC blockage, respectively. EnNaC at the endothelial cell surface was quantified by immunofluorescence staining. Cortical stiffness was monitored by atomic force microscopy when ambient sodium was raised from 135 to 150 mmol/L. In ex vivo aortae of older mice, endothelial cells had significantly higher EnNaC numbers than those of younger mice (+23%). In parallel, cortical stiffness was found increased (+8.5%). Acute application of high sodium led to an immediate rise in stiffness in both groups but was pronounced in endothelium of older mice (+18% versus +26%). Spironolactone and amiloride lowered EnNaC abundance and prevented endothelial stiffening under all conditions. We conclude that EnNaC mediates endothelial salt sensitivity in the aging process. This mechanism might contribute to the development of age-related cardiovascular disease and suggests the usage of spironolactone and amiloride specifically in the elderly.