Submitted on August 8, 2007
Accepted on January 8, 2008
Angiotensin-(1-7) serves as an aquaretic by increasing water intake and diuresis in association with down-regulation of aquaporin-1 during pregnancy in rats
JaNae Joyner1, Liomar AA Neves1, Kathyrn Stovall1, Carlos M Ferrario1, and K. Bridget Brosnihan1*
1 Hypertension and Vascular Research Center, Wake Forest University, Winston Salem, North Carolina, United States
* To whom correspondence should be addressed. E-mail: bbrosnih{at}wfubmc.edu.
We previously demonstrated that kidney and urine levels of angiotensin-(1-7) [Ang-(1-7)] were increased in pregnancy. To explore the role of Ang-(1-7) on fluid and electrolyte homeostasis during pregnancy, we evaluated the effect of the Ang-(1-7) antagonist D-Alanine-[Ang-(1-7)] (A-779) on kidney function. Virgin and pregnant rats received infusion of vehicle or A-779 (48µg/kg/hr) for 8 days by osmotic minipumps. Metabolic studies were done on treatment day 7-8. Virgin and pregnant rats at day 15 and 19 were sacrificed and blood and kidneys collected. Kidneys were prepared for western blot analysis for aquaporin-1 (AQP1) and aquaporin-2 (AQP2). In virgin female rats, A-779 increased urine volume and decreased urinary osmolality and AQP1 with no change in water intake. In 19d-pregnant rats, A-779 significantly decreased water intake and urine volume, and increased urinary osmolality and kidney AQP1 expression. Only in late gestation did A-779 treatment decrease the difference between intake and output (balance). A-779 treatment increased plasma vasopressin in late gestation but did not change vasopressin in virgins. In virgin and pregnant animals, A-779 administration had no effect on blood pressure, plasma volume, blood volume, or urinary electrolytes. These results suggest that Ang-(1-7) produces antidiuresis associated with up-regulation of AQP1 in virgin rats while Ang-(1-7) produces diuresis in late gestation with down-regulation of AQP1. Ang-(1-7) contributes to the enhanced water intake during pregnancy allowing maintenance of the normal volume expanded state despite diuresis produced in part by decreased AVP and AQP1.
