Angiotensin-(1-7) serves as an aquaretic by increasing water intake and diuresis in association with downregulation of aquaporin-1 during pregnancy in rats.
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 (48 microg.kg(-1).h(-1)) 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 killed, and blood and kidneys were collected. Kidneys were prepared for Western blot analysis for aquaporin-1 (AQP1) and aquaporin-2. In virgin female rats, A-779 increased urine volume and decreased urinary osmolality and AQP1 with no change in water intake. In 19-day 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 upregulation of AQP1 in virgin rats, whereas ANG-(1-7) produces diuresis in late gestation with downregulation 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.
Joyner
J
J
Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, NC 27157-1032, USA.
Neves
L A A
LA
Stovall
K
K
Ferrario
C M
CM
Brosnihan
K B
KB
D000803:Angiotensin I / Q000494:pharmacology*; D000818:Animals; D051398:Aquaporin 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D001794:Blood Pressure / Q000502:physiology; D015153:Blotting, Western; D003404:Creatinine / Q000097:blood; D004231:Diuresis / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D004326:Drinking / Q000187:drug effects*; D005260:Female; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D010953:Plasma Volume / Q000502:physiology; D011188:Potassium / Q000097:blood; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000097:blood; D014563:Urodynamics / Q000187:drug effects; D014667:Vasopressins / Q000097:blood; D014882:Water-Electrolyte Balance / Q000187:drug effects
D010446:Peptide Fragments; D014667:Vasopressins; D051398:Aquaporin 1; D000803:Angiotensin I; D012964:Sodium; D003404:Creatinine; C118790:angiotensin I (1-7); D011188:Potassium