G-protein-coupled receptor MAS deletion produces a preeclampsia-like phenotype in FVB/N mice

Abstract

Background - An unbalance in the renin-angiotensin (Ang) system between the Ang II/AT1 and Ang-(1-7)/Mas axis appears to be involved in preeclampsia (PE), in which a reduction of Ang-(1-7) was observed. Here we tested whether the reduction in the activity of the Ang-(1-7)/Mas axis could be a contributing factor for the development of PE, using Mas-deficient (Mas-/-) mice. Methods and Results - Cardiovascular parameters were evaluated by telemetry before, during pregnancy and 4 days post partum in twenty weeks old Mas-/- and wildtype (WT) female mice. Mas-/- mice presented reduced arterial blood pressure at baseline (91.3 ± 0.8 in Mas-/- vs. 94.0 ± 0.9 mmHg in WT, Diastolic, p<0.05). However, after the 13th day of gestation, blood pressure in Mas-/- mice started to increase, time-dependently, and at day 19 of pregnancy, these animals presented a higher blood pressure in comparison to WT group (90.5 ± 0.7 in Mas-/- vs. 80.3 ± 3.5 mmHg in WT, Diastolic D19, p<0.0001). Moreover, pregnant Mas-/- mice presented fetal growth restriction, increase in urinary protein excretion as compared to non-pregnant Mas-/- , oliguria, increase in cytokines, endothelial dysfunction and reduced ACE, AT1R, ACE2, ET-1A and eNOS placental mRNA, similar to some of the clinical manifestations found in the development of preeclampsia. Conclusions- These results show that Mas-deletion produces a preeclampsia-like state in FVB/N mice. Key Words: Mas-deficient mice - preeclampsia - Angiotensin-(1-7) / Mas axis