Endothelial sodium channels trigger endothelial salt sensitivity with aging.

Area of Science:

• Cardiovascular Physiology
• Aging Research
• Molecular Biology

Background:

• The epithelial sodium channel (EnNaC) is present in vascular endothelium, influencing endothelial cell mechanics and function.
• EnNaC activity correlates with endothelial dysfunction and salt sensitivity, conditions that worsen with age.

Purpose of the Study:

• To investigate the age-dependent changes in EnNaC abundance and its role in endothelial salt sensitivity.
• To explore the potential of EnNaC antagonism in mitigating age-related endothelial dysfunction.

Main Methods:

• Ex vivo analysis of aortae from young and old mice under varying sodium concentrations.
• Measurement of EnNaC abundance via immunofluorescence and cortical stiffness using atomic force microscopy.
• Pharmacological assessment using aldosterone antagonists (spironolactone) and EnNaC blockers (amiloride).

Main Results:

• Older mice exhibited significantly higher EnNaC numbers on endothelial cells compared to younger mice.
• Endothelial cortical stiffness increased with age and was exacerbated by high sodium, particularly in older mice.
• Spironolactone and amiloride reduced EnNaC levels and prevented sodium-induced stiffening.

Conclusions:

• EnNaC mediates endothelial salt sensitivity during the aging process.
• This EnNaC-driven mechanism may contribute to age-related cardiovascular diseases.
• Spironolactone and amiloride show potential therapeutic utility in the elderly for managing salt sensitivity and endothelial dysfunction.