Administration of D-alanine-[Ang-(1-7)] (A-779) prior to pregnancy in Sprague Dawley rats produces antidiuresis in late gestation

Abstract

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/hour after the start of pregnancy (gestational days 11 to 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 to 19) with vehicle or A-779 at a dose of 24 μg/kg/hour. Metabolic studies were completed in virgin animals and throughout pregnancy (gestational days 4 to 5, 14 to 15, and 18 to 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 days) 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 days), 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.