Abstract P308: Rgs2 Promotes Uterine Blood Flow During Pregnancy

Abstract

Regulators of G protein signaling (RGS) proteins are crucial in mediating vascular smooth muscle contraction via the regulation of heterotrimeric G proteins, affecting blood pressure and arterial blood flow. Previous studies by others and us showed that RGS2 deficiency augments vascular tone and impairs uterine blood flow (UBF) in non-pregnant mice, and that an Rgs2 loss-of-function mutation is linked to preeclampsia in humans; however, the mechanisms are unclear. Here, we tested the hypothesis that increased RGS2 expression and/or function facilitates placental perfusion by promoting vasodilation and UBF. We determined gene expression throughout pregnancy and post-partum period by real-time qPCR, while uterine blood flow and blood pressure were examined by ultrasound and carotid artery catheterization, respectively, under anesthesia. RGS2 expression decreased markedly by pregnancy day 10 (0.049 ± 0.013 vs. 0.023 ± 0.017) but returned to non-pregnancy level by day 15 (0.049 ± 0.013 vs. 0.041 ± 0.008,) in wild type mice. The pattern of changes in impedance to UBF mimicked gene expression profile in WT mice; in contrast, impedance remained elevated in Rgs2-/- mice at pregnancy day 15 (RI; WT: 0.516 ± 0.027, vs. RGS2-/-: 0.714 ± 0.020). Systemic blood pressure was similar between WT and Rgst2-/- mice at all stages of pregnancy. The results together indicate that RGS2 promotes uterine perfusion during pregnancy independently of its blood pressure effects. These findings are clinically relevant as selective targeting of G protein signaling could improve utero-placental hypoperfusion during pregnancy and prevent the development of pregnancy complications such as preeclampsia.