Sex and age result in differential regulation of the renal thiazide-sensitive NaCl cotransporter and the epithelial sodium channel in angiotensin II-infused mice.

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 (approximately 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 beta- and gamma-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.