Administration of D-Alanine-[Ang-(1-7)] (A-779) Prior to Pregnancy in Sprague Dawley Rats Produces Antidiuresis in Late Gestation.

We previously demonstrated that angiotensin-(1-7) [Ang-(1-7)], which is increased in the kidney and urine during pregnancy, influences normal fluid expansion of pregnancy. These previous studies were completed by chronic administration of the Ang-(1-7) receptor antagonist D-Alanine-[Ang-(1-7)] (A-779) at a dose of 48 μg/kg/hr after the start of pregnancy (gestational days 11-19). To further explore the role of Ang-(1-7) on kidney function during early, middle, and late pregnancy, Sprague Dawley rats were chronically pretreated 8 days prior to pregnancy and throughout pregnancy (gestational days 0-19) with vehicle or A-779 at a dose of 24 μg/kg/hr. Metabolic studies were completed in virgin animals and throughout pregnancy (gestational days 4-5, 14-15, and 18-19). Chow consumption and water intake increased throughout pregnancy while the difference between intake and output (balance) was increased only at late (day 19) pregnancy with both vehicle and A-779 administration. Urine volume and urinary osmolality were significantly increased and decreased respectively throughout pregnancy in vehicle treated rats only. In late (19 day) pregnancy, A-779 administration significantly decreased chow consumption and water intake. In virgin animals, A-779 administration significantly increased urine volume, while during late pregnancy (19 day), urine volume was significantly decreased with A-779 administration. These studies using pretreatment with a lower dose of A-779 prior to pregnancy confirm results of higher dose A-779 administration after the start of pregnancy. These studies show that Ang-(1-7) produces antidiuresis in virgin rats and diuresis in late gestation. Ang-(1-7) also contributes to the enhanced water intake during pregnancy allowing maintenance of the normal volume expanded state despite diuresis.