The endothelial αENaC contributes to vascular endothelial function in vivo

The Epithelial Sodium Channel (ENaC) is a key player in renal sodium homeostasis. The expression of α β γ ENaC subunits has also been described in the endothelium and vascular smooth muscle, suggesting a role in vascular function. We recently demonstrated that endothelial ENaC is involved in aldosterone-modulated endothelial stiffness. Here we explore the functional role of the endothelial αENaC subunit in vascular function in vivo. Compared to littermates, mice with conditional αENaC subunit gene inactivation in the endothelium only (endo-αENaC Knock Out mice) had no difference in their physiological parameters such as systolic blood pressure or heart rate. Acute and long-term renal Na+ handlings were not affected, indicating that endothelial αENaC subunit is not involved in renal sodium balance. Pharmacological inhibition of ENaC with benzamil blunted acetylcholine-induced nitric oxide production in mesenteric arteries from wild type mice but not in endo-αENaC KO mice, suggesting a critical role of endothelial ENaC in agonist-induced nitric oxide production. In endo-αENaC KO mice, compensatory mechanisms occurred and steady state vascular function was not altered except for flow-mediated dilation. Our data suggest that endothelial αENaC contributes to vascular endothelial function in vivo.

上皮钠通道（ENaC）是维持肾脏钠稳态的关键因素。α、β、γ ENaC 亚单位的表达亦见于内皮和血管平滑肌，暗示其在血管功能中扮演一定角色。近期，我们证实内皮 ENaC 参与了醛固酮调节的内皮刚度。本研究旨在探讨内皮 αENaC 亚单位在体内血管功能中的功能作用。与对照小鼠相比，仅在内皮中条件性灭活 αENaC 亚单位基因的小鼠（endo-αENaC 敲除小鼠）在生理参数如收缩压或心率上并无显著差异。急性及长期肾钠处理未受影响，表明内皮 αENaC 亚单位不参与肾脏钠平衡。使用苯氨咪对 ENaC 的药理抑制削弱了野生型小鼠肠系膜动脉中乙酰胆碱诱导的氮氧化物产生，但在 endo-αENaC 敲除小鼠中则无此效果，提示内皮 ENaC 在激动剂诱导的氮氧化物产生中发挥关键作用。在 endo-αENaC 敲除小鼠中，发生补偿机制，稳态血管功能未受影响，除血流介导的血管扩张外。我们的数据表明，内皮 αENaC 对体内血管内皮功能有所贡献。