High Salt Diet Affects Renal Sodium Excretion and ERRα Expression

Kidneys regulate the balance of water and sodium and therefore are related to blood pressure. It is unclear whether estrogen-related receptor alpha (ERR alpha), an orphan nuclear receptor and transcription factor highly expressed in kidneys, affects the reabsorption of water and sodium. The aim of this study was to determine whether changes in the expressions of ERR alpha, Na+/K+-ATPase and epithelial sodium channel (ENaC) proteins affected the reabsorption of water and sodium in kidneys of Dahl salt-sensitive (DS) rats. SS.13BN rats, 98% homologous to the DS rats, were used as a normotensive control group. The 24 h urinary sodium excretion of the DS and SS.13BN rats increased after the 6-week high salt diet intervention, while sodium excretion was increased in DS rats with daidzein (agonist of ERR alpha) treatment. ERR alpha expression was decreased, while beta- and gamma-ENaC mRNA expressions were increased upon high sodium diet treatment in the DS rats. In the chromatin immunoprecipitation (CHIP) assay, positive PCR signals were obtained in samples treated with anti-ERR alpha antibody. The transcriptional activity of ERR alpha was decreased upon high salt diet intervention. ERR alpha reduced the expressions of beta- and gamma-ENaC by binding to the ENaC promoter, thereby increased Na+ reabsorption. Therefore, ERR alpha might be one of the factors causing salt-sensitive hypertension.