Sex differences in adaptive downregulation of pre-macula densa sodium transporters with ANG II infusion in mice

Department of Medicine, Division of Endocrinology and Metabolism, Georgetown University, Washington, District of Columbia Submitted February 13, 2009 ; accepted in final form November 1, 2009 An increase in blood pressure (BP) due to angiotensin II (ANG II) infusion or other means is associated with adaptive pressure natriuresis due to reduced sodium reabsorption primarily in proximal tubule (PT) and thick ascending limb (TAL). We tested the hypothesis that male and female mice would show differential response to ANG II infusion with regard to the regulation of the protein abundance of sodium transporters in the PT and TAL and that these responses would be modulated by aging. Young ( 3 mo) and old ( 21 mo) male and female mice were infused with ANG II at 800 ng·kg body wt –1 ·min –1 by osmotic minipump for 7 days or received a sham operation. ANG II increased mean arterial pressure (MAP), measured by radiotelemetry, significantly more in male mice of both ages (increased 30–40 mmHg), compared with females (increased 15–25 mmHg). On day 1 , MAP was also significantly increased in old mice, relative to young ( P = 0.01). ANG II infusion was associated with a significant decline in plasma testosterone (to