The endothelial αENaC contributes to vascular endothelial function in vivo

Area of Science:

• Cardiovascular Physiology
• Renal Physiology
• Molecular Biology

Background:

• The Epithelial Sodium Channel (ENaC) plays a role in sodium homeostasis.
• ENaC subunits are expressed in vascular endothelium, suggesting a role in vascular function.
• Previous studies indicated endothelial ENaC involvement in aldosterone-modulated endothelial stiffness.

Purpose of the Study:

• To investigate the in vivo functional role of the endothelial αENaC subunit in vascular function.
• To determine if endothelial αENaC is involved in renal sodium balance and blood pressure regulation.
• To assess the impact of endothelial αENaC on agonist-induced nitric oxide production and vascular responses.

Main Methods:

• Generation of endothelial-specific αENaC knockout (endo-αENaC KO) mice.
• Measurement of physiological parameters including blood pressure and heart rate.
• Assessment of renal sodium handling.
• Pharmacological inhibition of ENaC using benzamil.
• Evaluation of acetylcholine-induced nitric oxide production in mesenteric arteries.
• Analysis of flow-mediated dilation.

Main Results:

• Endo-αENaC KO mice showed no differences in blood pressure, heart rate, or renal sodium handling compared to wild-type littermates.
• Pharmacological ENaC inhibition blunted acetylcholine-induced nitric oxide production in wild-type mice but not in endo-αENaC KO mice.
• Steady-state vascular function was maintained in endo-αENaC KO mice due to compensatory mechanisms, except for impaired flow-mediated dilation.

Conclusions:

• Endothelial αENaC is not essential for renal sodium balance or overall blood pressure regulation.
• Endothelial αENaC plays a critical role in agonist-induced nitric oxide production.
• Endothelial αENaC contributes to maintaining vascular endothelial function in vivo, particularly in flow-mediated responses.