Altered ENaC is Associated With Aortic Baroreceptor Dysfunction in Chronic Heart Failure

Area of Science:

• Cardiovascular Physiology
• Neuroscience
• Molecular Biology

Background:

• Abnormal baroreceptor function and reduced arterial baroreflex sensitivity are hallmarks of chronic heart failure (CHF).
• The epithelial sodium channel (ENaC) functions as a mechanosensor and is implicated in baroreceptor function.
• ENaC's role in baroreceptors of CHF models remains unclear.

Purpose of the Study:

• To investigate the expression and activation of ENaC in aortic baroreceptors of rats with surgically induced CHF.
• To determine if ENaC is altered in nodose neuronal cell bodies and aortic baroreceptor nerve terminals in CHF.

Main Methods:

• Chronic heart failure (CHF) was induced in rats via coronary artery ligation.
• Baroreceptor sensitivity was assessed hemodynamically.
• ENaC subunit expression (β, γ, α) was analyzed using immunostaining and Western blot.
• ENaC currents were measured in aortic baroreceptor neurons using whole-cell patch-clamp.

Main Results:

• CHF rats exhibited blunted aortic baroreceptor sensitivity compared to sham controls.
• β- and γ-ENaC subunits were detected in baroreceptors, while α-ENaC was undetectable.
• CHF significantly reduced β- and γ-ENaC protein expression in nodose neurons and nerve terminals.
• ENaC currents were significantly lower in aortic baroreceptor neurons of CHF rats.

Conclusions:

• Reduced ENaC expression and activation in aortic baroreceptors likely contribute to attenuated baroreflex sensitivity in CHF.
• Baroreceptors represent a potential therapeutic target for mitigating mortality in chronic heart failure.