Sildenafil Citrate Rescues Fetal Growth in the Catechol- <i>O</i> -Methyl Transferase Knockout Mouse Model

  • Joanna L. Stanley
    From the Department of Obstetrics and Gynecology (J.L.S., I.J.A., R.P., C.F.R.-C., S.T.D., P.N.B.) and Cardiovascular Research Centre (C.F.R.-C., S.T.D.), University of Alberta, Edmonton, Alberta, Canada; Maternal and Fetal Health Research Centre (C.P.S.), University of Manchester, Manchester, United Kingdom; Women's and Children's Health Research Institute (J.L.S., I.J.A., R.P., C.F.R.-C., S.T.D., P.N.B.), Edmonton, Alberta, Canada.
  • Irene J. Andersson
    From the Department of Obstetrics and Gynecology (J.L.S., I.J.A., R.P., C.F.R.-C., S.T.D., P.N.B.) and Cardiovascular Research Centre (C.F.R.-C., S.T.D.), University of Alberta, Edmonton, Alberta, Canada; Maternal and Fetal Health Research Centre (C.P.S.), University of Manchester, Manchester, United Kingdom; Women's and Children's Health Research Institute (J.L.S., I.J.A., R.P., C.F.R.-C., S.T.D., P.N.B.), Edmonton, Alberta, Canada.
  • Rajan Poudel
    From the Department of Obstetrics and Gynecology (J.L.S., I.J.A., R.P., C.F.R.-C., S.T.D., P.N.B.) and Cardiovascular Research Centre (C.F.R.-C., S.T.D.), University of Alberta, Edmonton, Alberta, Canada; Maternal and Fetal Health Research Centre (C.P.S.), University of Manchester, Manchester, United Kingdom; Women's and Children's Health Research Institute (J.L.S., I.J.A., R.P., C.F.R.-C., S.T.D., P.N.B.), Edmonton, Alberta, Canada.
  • Christian F. Rueda-Clausen
    From the Department of Obstetrics and Gynecology (J.L.S., I.J.A., R.P., C.F.R.-C., S.T.D., P.N.B.) and Cardiovascular Research Centre (C.F.R.-C., S.T.D.), University of Alberta, Edmonton, Alberta, Canada; Maternal and Fetal Health Research Centre (C.P.S.), University of Manchester, Manchester, United Kingdom; Women's and Children's Health Research Institute (J.L.S., I.J.A., R.P., C.F.R.-C., S.T.D., P.N.B.), Edmonton, Alberta, Canada.
  • Colin P. Sibley
    From the Department of Obstetrics and Gynecology (J.L.S., I.J.A., R.P., C.F.R.-C., S.T.D., P.N.B.) and Cardiovascular Research Centre (C.F.R.-C., S.T.D.), University of Alberta, Edmonton, Alberta, Canada; Maternal and Fetal Health Research Centre (C.P.S.), University of Manchester, Manchester, United Kingdom; Women's and Children's Health Research Institute (J.L.S., I.J.A., R.P., C.F.R.-C., S.T.D., P.N.B.), Edmonton, Alberta, Canada.
  • Sandra T. Davidge
    From the Department of Obstetrics and Gynecology (J.L.S., I.J.A., R.P., C.F.R.-C., S.T.D., P.N.B.) and Cardiovascular Research Centre (C.F.R.-C., S.T.D.), University of Alberta, Edmonton, Alberta, Canada; Maternal and Fetal Health Research Centre (C.P.S.), University of Manchester, Manchester, United Kingdom; Women's and Children's Health Research Institute (J.L.S., I.J.A., R.P., C.F.R.-C., S.T.D., P.N.B.), Edmonton, Alberta, Canada.
  • Philip N. Baker
    From the Department of Obstetrics and Gynecology (J.L.S., I.J.A., R.P., C.F.R.-C., S.T.D., P.N.B.) and Cardiovascular Research Centre (C.F.R.-C., S.T.D.), University of Alberta, Edmonton, Alberta, Canada; Maternal and Fetal Health Research Centre (C.P.S.), University of Manchester, Manchester, United Kingdom; Women's and Children's Health Research Institute (J.L.S., I.J.A., R.P., C.F.R.-C., S.T.D., P.N.B.), Edmonton, Alberta, Canada.

この論文をさがす

説明

<jats:p> Preeclampsia and fetal growth restriction are responsible for the majority of maternal and perinatal morbidity and mortality associated with complicated pregnancies. Although their etiologies are complex and multifactorial, both are associated with increased uterine artery resistance. Sildenafil citrate is able to rescue the dysfunction observed ex vivo in uterine arteries of women with preeclampsia. The ability of sildenafil citrate to increase uterine artery vasodilation, thereby decreasing uterine artery resistance and, hence, ameliorated preeclampsia and fetal growth restriction, was tested in a mouse model of preeclampsia, the catechol- <jats:italic>O</jats:italic> -methyl transferase knockout mouse (COMT <jats:sup>−/−</jats:sup> ). COMT <jats:sup>−/−</jats:sup> and C57BL/6J mice were treated (0.2 mg/mL in drinking water, n=6–12) from gestational day 12.5 to 18.5. Measures of pup growth, including body weight, crown/rump length, and abdominal circumference, were reduced in COMT <jats:sup>−/−</jats:sup> mice; this was normalized after treatment with Sildenafil. COMT <jats:sup>−/−</jats:sup> mice also demonstrated abnormal umbilical Doppler waveforms, including reverse arterial blood flow velocity. This was normalized after treatment with Sildenafil. Abnormal uterine artery Doppler waveforms were not demonstrated in COMT <jats:sup>−/−</jats:sup> mice, although ex vivo responses of uterine arteries to phenylephrine were increased; moreover, treatment with Sildenafil did improve ex vivo sensitivity to an endothelium-dependent vasodilator. The data presented here demonstrate that Sildenafil can rescue pup growth and improve abnormal umbilical Doppler waveforms, providing support for a potential new therapeutic strategy targeting fetal growth restriction. </jats:p>

収録刊行物

  • Hypertension

    Hypertension 59 (5), 1021-1028, 2012-05

    Ovid Technologies (Wolters Kluwer Health)

被引用文献 (5)*注記

もっと見る

詳細情報 詳細情報について

問題の指摘

ページトップへ