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Abstract: FR-PO195

The Rapid Membrane Insertion of the Endothelial Sodium Channel Is Induced by Shear Stress and Stiffens the Cell Cortex

Session Information

Category: Hypertension

  • 1103 Vascular Biology and Dysfunction


  • Kusche-Vihrog, Kristina, University of Muenster, Muenster, Germany

The endothelial Na+ channel (EnNaC) determines endothelial nanomechanics in that an increased membrane abundance of EnNaC stiffens the endothelial cell cortex. Surface EnNaC expression is mainly regulated by aldosterone via the mineralocorticoid receptor (MR). Endothelial cells are constantly exposed to wall shear stress by blood flow, whereas disturbed blood flow causes and maintains atherosclerotic processes. Here, it is hypothesized that EnNaC serves as a flow sensor. Thus, we tested whether laminar shear stress (LSS) and non-laminar shear stress (NLSS) influence EnNaC membrane abundance and endothelial stiffness.


LSS (8 dyne/cm2) was applied by a shear stress pump on HUVECs seeded on slides with and without branching regions in the presence of 1nM aldosterone to simulate blood flow. After applying shear stress (chronic 48h and acute 15min) HUVECs were fixed. EnNaC membrane abundance was quantified by a Quantum Dot-based immunofluorescence approach. Cortical stiffness was monitored using nanoindentation measurements via atomic force microscopy (AFM) in LSS and NLSS regions of the slides.


Under chronic shear stress (48h) a significant increase of membrane EnNaC was found. Importantly, already after 15 min. LSS αEnNaC membrane abundance was increased by 58.5±4.5%. Both (i) inhibition of exocytosis with Brefeldin A and (ii) (ii) MR antagonism with Canrenone, could prevent the acute shear stress-induced EnNaC membrane insertion indicating a rapid MR-mediated effect of shear stress. EnNaC membrane abundance under NLSS in branching regions was also significantly increased compared to static controls (+24.9±4.3%). AFM measurements revealed that the shear stress-induced increase in EnNaC lead to stiffening of the cell cortex by 18.9±5.5% compared to static controls.


Our results suggest that EnNaC, besides being a mechano-sensor, is regulated by shear stress. Since both chronic and acute shear stress increase the membrane abundance we postulate genomic and non-genomic mechanisms leading to the MR-dependent membrane insertion of EnNaC and subsequent endothelial stiffening. These changes in nanomechanics and thus endothelial function might be a physiological response to changes in hemodynamics and further explain the atherogenic potential of disturbed blood flow.


  • Government Support - Non-U.S.