Sex and Age Result in Differential Regulation of the Renal Thiazide-Sensitive NaCl Cotransporter and the Epithelial Sodium Channel in Angiotensin II-Infused Mice

Abstract Background/Aims: We determined the effects of age and sex on the blood pressure (BP) response to angiotensin II (Ang II) infusion and evaluated the potential mechanistic role of the thiazide-sensitive NaCl cotransporter (NCC) and the epithelial sodium channel (ENaC). Methods: Male and female mice (∼3 or 21 months of age) were infused with Ang II or control for 7 days. Results: Males had a greater BP response to Ang II, somewhat enhanced by aging. Mean systolic BPs (at 7 days) were (mm Hg): 161, 143, 172, and 157 in young male, young female, old male, and old female mice, respectively. Immunoblotting changes in the whole kidney that supported this BP profile included a 51 and 52% increase in NCC band density in the old females and old males (as compared to sex-respective controls) with Ang II infusion, while the young males and young females showed an increase of 40 and 0%, respectively. Young males also had a greater reduction in major bands of β- and γ-ENaC, than did young female mice. The natriuretic response to hydrochlorothiazide supported an increase in activity of NCC with Ang II in aged mice only. Conclusions: Increased sensitivity to Ang II in aging and male mice may involve overactivity of NCC.