| First Author | Jie L | Year | 2016 |
| Journal | Physiol Rep | Volume | 4 |
| Issue | 2 | PubMed ID | 26811058 |
| Mgi Jnum | J:351720 | Mgi Id | MGI:6873292 |
| Doi | 10.14814/phy2.12692 | Citation | Jie L, et al. (2016) RGS2 squelches vascular Gi/o and Gq signaling to modulate myogenic tone and promote uterine blood flow. Physiol Rep 4(2):e12692 |
| abstractText | 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 Gq/11 and Gi/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 Ca(2+) 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 Gi/o and Gq 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. |
