Epithelial Na+ channel and the glycocalyx: a sweet and salty relationship for arterial shear stress sensing

Curr Opin Nephrol Hypertens. 2022 Mar 1;31(2):142-150. doi: 10.1097/MNH.0000000000000779.

Abstract

Purpose of review: The ability of endothelial cells to sense mechanical force, and shear stress in particular, is crucial for normal vascular function. This relies on an intact endothelial glycocalyx that facilitates the production of nitric oxide (NO). An emerging arterial shear stress sensor is the epithelial Na+ channel (ENaC). This review highlights existing and new evidence for the interdependent activity of the glycocalyx and ENaC and its implications for vascular function.

Recent findings: New evidence suggests that the glycocalyx and ENaC are physically connected and that this is important for shear stress sensing. The connection relies on N-glycans attached to glycosylated asparagines of α-ENaC. Removal of specific N-glycans reduced ENaC's shear stress response. Similar effects were observed following degradation of the glycocalyx. Endothelial specific viral transduction of α-ENaC increased blood pressure (∼40 mmHg). This increase was attenuated in animals transduced with an α-ENaC version lacking N-glycans.

Summary: These observations indicate that ENaC is connected to the glycocalyx and their activity is interdependent to facilitate arterial shear stress sensation. Future research focusing on how N-glycans mediate this interaction can provide new insights for the understanding of vascular function in health and disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Endothelial Cells / metabolism
  • Epithelial Sodium Channels* / metabolism
  • Glycocalyx* / metabolism
  • Humans
  • Polysaccharides / metabolism
  • Sodium / metabolism
  • Stress, Mechanical

Substances

  • Epithelial Sodium Channels
  • Polysaccharides
  • Sodium