Epithelial sodium channel stiffens the vascular endothelium in vitro and in liddle mice

Pia Jeggle, Chiara Callies, Antoine Tarjus, Celine Fassot, Johannes Fels, Hans Oberleithner, Frederic Jaisser, Kristina Kusche-Vihrog*

*Corresponding author for this work
62 Citations (Scopus)


Liddle syndrome, an inherited form of hypertension, is caused by gain-of-function mutations in the epithelial Na channel (ENaC), the principal mediator of Na reabsorption in the kidney. Accordingly, the disease pathology was ascribed to a primary renal mechanism. Whether this is the sole responsible mechanism, however, remains uncertain as dysregulation of ENaC in other tissues may also be involved. Previous work indicates that ENaC in the vascular endothelium is crucial for the regulation of cellular mechanics and thus vascular function. The hormone aldosterone has been shown to concomitantly increase ENaC surface expression and stiffness of the cell cortex in vascular endothelial cells. The latter entails a reduced release of the vasodilator nitric oxide, which eventually leads to an increase in vascular tone and blood pressure. Using atomic force microscopy, we have found a direct correlation between ENaC surface expression and the formation of cortical stiffness in endothelial cells. Stable knockdown of αENaC in endothelial cells evoked a reduced channel surface density and a lower cortical stiffness compared with the mock control. In turn, an increased αENaC expression induced an elevated cortical stiffness. More importantly, using ex vivo preparations from a mouse model for Liddle syndrome, we show that this disorder evokes enhanced ENaC expression and increased cortical stiffness in vascular endothelial cells in situ. We conclude that ENaC in the vascular endothelium determines cellular mechanics and hence might participate in the control of vascular function.

Original languageEnglish
Issue number5
Pages (from-to)1053-1059
Number of pages7
Publication statusPublished - 05.2013

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)


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