Sex and Age Differences in Renal Ability to Conserve Water and Sodium in F344 x Brown Norway Rats

Abstract

Renal sodium and water concentrating ability declines with age. The potential role of sex differences in the regulation of sodium and water transport proteins with aging has not been determined. To address this, male and female Fisher 344 X Brown Norway (F344BN) rats were studied at 3 months (young) and 30 months (aged) of age, while on a sodium deficient (NaD, Na+ content <0.005%) or a control (C, Na+ content = 0.4%) diet. Urine volume and sodium were increased and urine osmolality was decreased in aged female vs. aged male rats on both diets, but there were no significant differences in these parameters between young males and females. Vasopressin V2 receptor (V2R) and AQP2 protein abundances in the kidney inner medulla were markedly decreased in aged female vs. aged male rats on both diets. The thiazide-sensitive NaCl co-transporter (NCC) abundance in the cortex (CTX) was significantly increased in young females vs. males on C diet. Although the NaD-induced increase of NCC in CTX was blunted with aging, there were no significant differences between males and females on NaD. α-epithelial sodium channel (ENaC) abundance in CTX was similarly increased in females vs. males, but equivalent increases on NaD diet were observed in both young and aged rats. This was true for the 70 kDa band of γ-ENaC as well. In conclusion, relatively down-regulated kidney V2R and AQP2 abundances may contribute to reduced urine concentration in aged female vs. aged male rats. However, the impaired urinary sodium conservation on NaD diet in aged female rats does not appear to be the result of reduced abundances of distal sodium transporters and sodium channel subunits.