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Journal article
RGS2 squelches vascular G(i/o) and G(q) signaling to modulate myogenic tone and promote uterine blood flow
Physiological reports, v 4(2)
01 Jan 2016
PMID: 26811058
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Uterine artery blood flow (UABF) is critical to maintaining uterine perfusion in nonpregnant states and for uteroplacental delivery of nutrients and oxygen to the fetus during pregnancy. Impaired UABF is implicated in infertility and several pregnancy complications including fetal growth restriction, small for gestational age, and preeclampsia. The etiology of abnormal UABF is not known. Here, we determined whether deficiency or loss of RGS2, a GTPase-activating protein for G(q/11) and G(i/o) class G proteins, affects UABF in nonpregnant mice. We used Doppler ultrasonography to assess UABF in wild type (WT), Rgs2 heterozygous (Rgs2+/-), and homozygous knockout (Rgs2-/-) mice. Video microscopy was used for ex vivo examination of uterine artery myogenic tone and fura-2 imaging for in vitro assessment of internal stores Ca2+ release. We found that baseline UABF velocity was markedly decreased while impedance measured as resistive index (WT = 0.58 +/- 0.04 vs. Rgs2-/- = 0.71 +/- 0.03, P < 0.01) and pulsatile index (WT = 0.90 +/- 0.06 vs. Rgs2-/- = 1.25 +/- 0.11, P < 0.01) was increased in Rgs2-/- mice. Uterine artery tone was augmented in Rgs2+/- and Rgs2-/- mice, which was normalized to WT levels following G(i/o) and G(q) inactivation. Conversely, blockade of ryanodine receptors increased WT myogenic tone to RGS2 mutant levels. The data together indicate that RGS2 deficiency decreases UABF by increasing myogenic tone at least partly through prolonged G protein activation. Mutations that decrease vascular RGS2 expression may be a predisposition to decreased uterine blood flow. Targeting G protein signaling therefore might improve uterine and uteroplacental underperfusion disorders.
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Details
- Title
- RGS2 squelches vascular G(i/o) and G(q) signaling to modulate myogenic tone and promote uterine blood flow
- Creators
- Li Jie - Drexel UniversityElizabeth A. Owens - Drexel UniversityLauren A. Plante - Drexel UniversityZhuyuan Fang - Jiangsu Provincial Hospital of Traditional Chinese MedicineDerek T. Rensing - Washington University in St. LouisKevin D. Moeller - Washington University in St. LouisPatrick Osei-Owusu - Drexel University
- Publication Details
- Physiological reports, v 4(2)
- Publisher
- Wiley
- Number of pages
- 13
- Grant note
- Drexel University College of Medicine CBET 1262176 / National Science Foundation; National Science Foundation (NSF) Margaret Q. Landenberger Research Foundation 1262176 / Div Of Chem, Bioeng, Env, & Transp Sys; National Science Foundation (NSF); NSF - Directorate for Engineering (ENG)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000380235200010
- Scopus ID
- 2-s2.0-85005996145
- Other Identifier
- 991019167768104721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Physiology