Role of epithelial Na+ channels in endothelial function

Dongqing Guo, Shenghui Liang, Su Wang, Chengchun Tang, Bin Yao, Wenhui Wan, Hailing Zhang, Hui Jiang, Asif Ahmed, Zhiren Zhang, Yuchun Gu*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

An increasing number of mechano-sensitive ion channels in endothelial cells have been identified in response to blood flow and hydrostatic pressure. However, how these channels respond to flow under different physiological and pathological conditions remains unknown. Our results show that epithelial Na+ channels (ENaCs) colocalize with hemeoxygenase-1 (HO-1) and hemeoxygenase-2 (HO-2) within the caveolae on the apical membrane of endothelial cells and are sensitive to stretch pressure and shear stress. ENaCs exhibited low levels of activity until their physiological environment was changed; in this case, the upregulation of HO-1, which in turn facilitated heme degradation and hence increased the carbon monoxide (CO) generation. CO potently increased the bioactivity of ENaCs, releasing the channel from inhibition. Endothelial cells responded to shear stress by increasing the Na+ influx rate. Elevation of intracellular Na+ concentration hampered the transportation of l-arginine, resulting in impaired nitric oxide (NO) generation. Our data suggest that ENaCs that are endogenous to human endothelial cells are mechano-sensitive. Persistent activation of ENaCs could inevitably lead to endothelium dysfunction and even vascular diseases such as atherosclerosis.

Original languageEnglish
Pages (from-to)290-297
Number of pages8
JournalJournal of Cell Science
Volume129
Issue number2
Early online date30 Nov 2015
DOIs
Publication statusPublished - 1 Jan 2016

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Bibliographical note

© 2016. Published by The Company of Biologists Ltd. Non-commercial use only

Keywords

  • ENaC
  • endothelium dysfunction
  • heme
  • mechanical stress
  • NO

Cite this

Guo, D., Liang, S., Wang, S., Tang, C., Yao, B., Wan, W., Zhang, H., Jiang, H., Ahmed, A., Zhang, Z., & Gu, Y. (2016). Role of epithelial Na+ channels in endothelial function. Journal of Cell Science, 129(2), 290-297. https://doi.org/10.1242/jcs.168831