Department of Physiology, School of Biomedical Sciences (P.P., I.v.H., F.J.M., M.F.), University of Otago, Dunedin, New Zealand.
HeartOtago (P.P., I.v.H., S.C., M.F.), University of Otago, Dunedin, New Zealand.
Hypertension. 2022 Jul;79(7):1385-1394. doi: 10.1161/HYPERTENSIONAHA.122.18924. Epub 2022 May 5.
Elevated expression and increased activity of vascular epithelial sodium channel (ENaC) can result in vascular dysfunction in small animal models. However, there is limited or no knowledge on expression and function of ENaC channels in human vasculature. Hence, this study explored the expression and function of ENaC in human arteries and their association with hypertension.
Human internal mammary artery (IMA) and aorta were obtained from cardiovascular patients undergoing coronary artery bypass graft surgery. Expression of the ENaC subunit was analyzed by polymerase chain reaction, Western blot, and immunohistochemistry. ENaC function was observed by patch-clamp electrophysiology in endothelial cells isolated from IMA. Levels of ENaC subunit expression levels were compared between arteries from normotensive, uncontrolled hypertensive, and controlled hypertensive patients.
For the first time, expression of α, β, γ, and δ was detected at mRNA and protein levels in human IMA and aorta. Single-channel patch-clamp recordings identified both αβγ- and δβγ-like channel conductance in primary endothelial cells isolated and cultured from IMA. Reduced expression of the δ subunit was observed in controlled hypertensive IMA, whereas reduced expression of γ-ENaC was observed in controlled hypertensive aorta.
These data suggest that functional ENaC channels are expressed in human arteries and their expression levels are associated with hypertension.
血管上皮钠通道（ENaC）的表达升高和活性增加可导致小动物模型中的血管功能障碍。然而，关于 ENaC 通道在人血管中的表达和功能知之甚少或没有。因此，本研究探讨了 ENaC 在人动脉中的表达和功能及其与高血压的关系。
从接受冠状动脉旁路移植术的心血管病患者中获得人内乳动脉（IMA）和主动脉。通过聚合酶链反应、Western blot 和免疫组织化学分析 ENaC 亚基的表达。通过从 IMA 分离的内皮细胞的膜片钳电生理学观察 ENaC 的功能。比较正常血压、未控制高血压和控制高血压患者动脉中 ENaC 亚基表达水平。
首次在人 IMA 和主动脉中检测到 mRNA 和蛋白水平的 α、β、γ 和 δ 的表达。从 IMA 分离和培养的原代内皮细胞中的单通道膜片钳记录鉴定了 αβγ-和 δβγ 样通道电导。在控制良好的高血压 IMA 中观察到 δ 亚基的表达减少，而在控制良好的高血压主动脉中观察到 γ-ENaC 的表达减少。
这些数据表明，功能性 ENaC 通道在人动脉中表达，其表达水平与高血压有关。
