Sex Differences in Renal Sodium Transporter Gene Expression

Abstract

Regulation of sodium balance and blood volume by the kidneys is an important determinant of blood pressure control. Although the causative mechanisms remain unclear, it is well established that male sex is associated with higher blood pressure and increased cardiovascular risk compared to female sex. In order to determine a possible role for renal sodium transporters in sex‐dependent blood pressure regulation, we examined a number of renal transport genes in the kidney cortex of male and female mice. Under normal conditions, the circadian clock protein Per1 is a positive regulator of sodium transport genes including αENaC (α subunit of the epithelial sodium channel), Wnk1(with‐no‐lysine kinase 1), and NCC (sodium‐chloride cotransporter). Using qPCR and western blot analysis, we found significant differences between the sexes in a number of renal sodium transport genes and clock genes. Interestingly, Per1 (Period 1), Sgk1 (serum and glucocorticoid kinase 1), αENaC, Edn‐1 (Endothelin‐1), and NCC expression was higher in females compared to males whereas Wnk1 expression was equivalent between the sexes. These data show significant sex‐dependent differences in gene expression of distinct sodium transport genes and circadian clock genes. Whether or not these differences are related to sex‐dependent differences in blood pressure remains to be determined.Support or Funding InformationThis work was supported by NIH DK085193 and DK098460, the ASN Foundation for Kidney Research to MLG and 2T32HL083810 to KS.