Angiotensin‐(1–7) increases water intake and produces diuresis in association with down‐regulation of aquaporin‐1 during pregnancy in rats

Abstract

Previous studies showed that kidney and urine levels of angiotensin-(1–7) [Ang-(1–7)] were increased in pregnancy (PR). Since the role of Ang-(1–7) on fluid and electrolyte homeostasis during PR has not been explored, we evaluated the effect of the Ang-(1–7) antagonist A-779 on kidney function. Virgin and PR rats at gestational day 7 and 11 received infusion of vehicle or Ang-(1–7) antagonist A-779 (48μg/kg/hr) for 8 days by osmotic minipumps. Metabolic studies were completed on treatment day 7–8. Virgin and PR at day 15 and 19 were sacrificed and kidneys were prepared for western blot analysis using polyclonal antibodies for AQP1 and AQP2. Urine volume increased progressively throughout gestation in vehicle, but not in A-779 treated rats. In 19d-PR rats, A-779 as compared to vehicle significantly decreased urine volume (19 ± 2 vs 28 ± 2 mL/24hr, p<0.05), increased urinary osmolality (1038 ± 80 vs 844 ± 66 mOsm/L, p<0.05), and decreased water intake (37 ± 3 vs 53 ± 3 ml/24hr, p<0.05), but had no effect on urinary sodium and potassium excretion. AQP1 kidney expression (28kDa) (15 ± 6 vs 4 ± 1 ROD, p<0.05) was significantly increased in A-779 treated 19d-PR rats without a change in AQ2 (29kDa). These studies suggest that Ang-(1–7) increases water intake and produces diuresis during late pregnancy by decreasing water reabsorption through down-regulation of the kidney AQP1 water channel. Sponsored by HL051952; AHA0615416