期刊
PHYSIOLOGICAL REPORTS
卷 4, 期 2, 页码 -出版社
WILEY
DOI: 10.14814/phy2.12692
关键词
G protein signaling; myogenic tone; calcium; RGS2; uterine blood flow
类别
资金
- Drexel University College of Medicine
- Margaret Q. Landenberger Research Foundation
- National Science Foundation [CBET 1262176]
- Div Of Chem, Bioeng, Env, & Transp Sys
- Directorate For Engineering [1262176] Funding Source: National Science Foundation
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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