Elevated Blood Pressure and Abnormal Evolution of Pregnancy in ACE2‐Deficient Female Mice

Angiotensin‐converting enzyme 2 (ACE2) generates Ang‐(1–7) which interacts with Mas. We have recently observed that pregnant Mas‐ deficient − mice presented a preeclampsia‐like state. However, it is not clear whether this effect is caused by a reduction of the activity of the ACE2/Ang‐(1–7)/ Mas axis or other Mas ‐dependent actions. Here we evaluated the phenotypic alterations induced by ACE2 deficiency during pregnancy in C57Bl/6 mice (ACE2 −/− ). Twenty weeks old ACE2 −/− and WT female mice were used. Blood pressure was measured by telemetry before, during pregnancy and 4 days after delivery. Female ACE2 −/− mice presented increased MAP before pregnancy (106±1 in ACE2 −/− vs. 99±2 mmHg in WT). During pregnancy, ACE2 −/− MAP remained constant with only small fluctuations. However, after delivery, MAP decreased in WT, but not in ACE2 −/− KO (108.7±1 mmHg in ACE2 −/− vs. 97±1 in WT). The ACE2 −/− mice also presented a significant reduction in body weight after delivery and the ACE2 −/− pups showed fetal growth restriction (1.33±0.03 g in ACE2 −/− vs. 1.49±0.01 g in WT). More interesting, ACE2 −/− mothers had a significant number of dead pups presenting developmental abnormalities. These data show, for the first time, that ACE2 plays a critical role in fetal development. In addition, our data further support an important role of the ACE2/Ang‐(1–7)/Mas axis in the hemodynamic adjustment during pregnancy. Support: CAPES – PROBRAL