Abstract 1755: G-Protein-Coupled Receptor MAS Deficiecy is Involved in Preeclampsia
Preeclampsia, a multisystemic syndrome, is an important cause of maternal and fetal morbidity and mortality. A mismatch between the vasoconstrictor peptide, Ang II and the vasodilator Ang-(1–7)/Mas axis may lead to vasoconstriction and endothelial dysfunction. Moreover, Ang-(1–7) is decreased in preeclamptic patients. However it is not clear whether the reduction in the activity of the Ang-(1–7)/Mas axis is a contributing factor for development of preeclampsia. The aim of this study was to evaluate whether Mas-deficiency is involved in pregnancy-induced hypertension. Thirteen weeks old Mas−/− and WT female mice were used. Values of blood pressure versus pregnancy time were measured. After anesthesia by inhalation of 2% isoflurane, pups were collected and weighted. Pregnant Mas−/− mice presented increased blood pressure (96 ± 3 before fertilization to 129 ± 5 on 18th day in KO and 95 ± 3 before fertilization to 111 ± 7 mmHg at day 18 in WT), associated with 36% intrauterine growth restriction when compared to WT mice. In addition, significant increases in microalbuminuria, 6-Interleukin levels and vascular dysfunction indicated by increase vasoreactivity to phenylephrine and blunted vasorelaxation to acetylcholine were observed. In order to ascertain whether changes in placental Mas expression would be also associated with preeclampsia, 96 women were separated into two groups: third trimester preeclamptic women (n = 55) and third trimester normotensive, healthy women (n = 41). All women underwent Doppler examination (Sonoace 8800) of uterine arteries resistance index (uterine RI), umbilical artery pulsatility index (umbilical PI) and cerebral - umbilical artery pulsatility index (C/U) at third trimester of gestation. Moreover, placental tissues (80 μg of protein) were analyzed by western blotting for the Ang-(1–7) receptor Mas expression. Preeclamptic patients presented a significant reduction of the Ang-(1–7) receptor Mas expression when compared to normotensive patients (p = 0.041) in parallel with the increased umbilical PI (p = 0.033) and C/U I (p = 0.033). These results indicate that decreased activity of the Ang-(1–7)/Mas axis is a contributing factor in the development of pregnancy-induced hypertension.