High Salt Diet Affects Renal Sodium Excretion and ERRα Expression

Area of Science:

• Nephrology
• Endocrinology
• Molecular Biology

Background:

• Kidneys are crucial for blood pressure regulation via water and sodium balance.
• The role of estrogen-related receptor α (ERRα) in kidney water and sodium reabsorption remains unclear.
• ERRα is an orphan nuclear receptor and transcription factor highly expressed in the kidneys.

Purpose of the Study:

• To investigate the impact of ERRα, Na⁺/K⁺-ATPase, and epithelial sodium channel (ENaC) protein expression changes on kidney water and sodium reabsorption.
• To determine the role of ERRα in salt-sensitive hypertension using Dahl salt-sensitive (DS) rats and normotensive SS.13BN rats.

Main Methods:

• High salt diet intervention in DS and SS.13BN rats.
• Daidzein treatment (ERRα agonist) in DS rats.
• Measurement of 24-hour urinary sodium excretion.
• Analysis of ERRα, Na⁺/K⁺-ATPase, and ENaC (β- and γ-subunits) mRNA and protein expression.
• Chromatin immunoprecipitation (CHIP) assay to assess ERRα binding to the ENaC promoter.

Main Results:

• High salt diet increased urinary sodium excretion in both DS and SS.13BN rats.
• Daidzein treatment increased sodium excretion in DS rats.
• High sodium diet decreased ERRα expression and increased β- and γ-ENaC mRNA in DS rats.
• CHIP assay confirmed ERRα binding to the ENaC promoter.
• ERRα transcriptional activity decreased with high salt diet.
• ERRα was found to reduce β- and γ-ENaC expression, thereby increasing Na+ reabsorption.

Conclusions:

• ERRα negatively regulates the expression of β- and γ-ENaC by binding to their promoter.
• Reduced ERRα activity or expression leads to increased sodium reabsorption.
• ERRα may be a contributing factor in the development of salt-sensitive hypertension.