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. Copyright 2009 S. Karger AG, Basel.
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. Copyright 2009 S. Karger AG, Basel.
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