Attenuated Function of Angiotensin-(1-7) in Placental Artery During Preeclampsia not through MAS1 Receptor

Abstract

\n Background: As a counter-regulatory component of the renin-angiotensin-system (RAS), the angiotensin-(1–7) [Ang-(1–7)] plays a protective role in cardiovascular diseases. However, the association between Ang-(1–7) and preeclampsia in humans is unclear. Methods: Experiments were conducted in the placentas and peripheral blood collected from 32 women with normal pregnancy and 20 women with preeclampsia.Results: The vasocontractions induced by Ang II were significantly inhibited by Ang-(1-7) in the normal placental artery (P<0.001) but not in the preeclampsia group. Treatment with A779 (MAS1R inhibitor) and PD (AT2R inhibitor) could not block the inhibitory effect of Ang-(1-7) on Ang II-induced vasoconstriction. Real-time quantitative PCR indicated that the mRNA levels of AT1R was significantly decreased (P<0.001) in preeclamptic group. In Hematoxylin-Eosin (HE) staining experiment, the placental artery in preeclamptic group were with a greater wall thickness and a smaller luminal area than those in normal group. In addition, as the consequence of the activation of β-arrestin pathway, the phosphorylation level of ERK protein was significantly reduced (P<0.01) in the nucleus and significantly increased (P<0.05) in the cytoplasm of placental vascular tissue in preeclamptic group. Discussion: Together, these data indicated that Ang-(1-7) antagonizes the function of Ang II in placenta vessels of normal pregnant women, but this effect is obviously eliminated in preeclampsia. Treatment with A779 and PD indicated that Ang-(1-7) may not exert its effect through MAS1R and AT2R. Persistent activation of the β-arrestin pathway and the weaken function of Ang-(1-7) in placental artery might contribute to the pathogenesis of preeclampsia.