Significance The ability to sense mechanical forces is essential for all living organisms. Extracellular tethers have been proposed to mediate mechanical activation of channels belonging to the epithelial Na ⁺ channel (ENaC)/degenerin protein family. The nature and architecture of the tethers that link the channel protein with the extracellular matrix are unknown. Our study provides experimental evidence that glycosylated asparagines and their N -glycans are part of tethers for mechanical activation of ENaC by shear force. The identified asparagines are also important for arterial blood pressure regulation in vivo. These findings provide insights into how mechanical forces are sensed by mechanosensitive ENaC channels to regulate blood pressure.