Miho Miyakawa

Juntendo University, Edo, Tokyo, Japan

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Publications (4)3.65 Total impact

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    ABSTRACT: A low-protein diet (LPD) during pregnancy induces vascular dysfunction and hypertension in the offspring, prevented by administration of an angiotensin II type 1 (AT(1)) receptor antagonist in early life to the offspring. Whether such protection extends to subsequent pregnancy is unknown; we therefore hypothesized that administration of a specific AT(1) receptor antagonist (losartan) in early life to offspring of LPD dams would improve vascular dysfunction in their uterine arteries when they, in turn, were pregnant. Pregnant rats were randomly divided into two dietary groups fed a control (C) or protein-restricted (R) diet throughout pregnancy. Between two and 10 weeks postnatally, female offspring (F(1)) were randomly assigned to drink either pure tap water (CO, RO) or water with losartan (CL, RL). Offspring were mated and killed on gestational day 19 or 20 in order to investigate uterine artery function. In pregnant offspring, vasoconstriction of the uterine arteries to phenylephrine (PE) and the thromboxane A2 mimetic U46619 was greater in RO than CO (F(1)). Responses to both antagonists were suppressed in RL (F(1)). Relaxation to sodium nitroprusside was increased in RO versus CO and suppressed in RL versus RO (F(1)). Administration of an AT(1) receptor antagonist to offspring during the suckling and juvenile period improves the uterine vascular dysfunction in pregnancy induced by prior maternal LPD during their development. Such treatment may contribute to decreasing the transmitted risks of maternal malnutrition from offspring to the subsequent generation.
    No preview · Article · Mar 2012 · Journal of Obstetrics and Gynaecology Research
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    ABSTRACT: Our previous study showed that a maternal low-protein diet induced hypertension and vascular dysfunction in rat offspring after day 175. In the present study, we hypothesized that these female offspring would develop hypertension in their own pregnancies even at ages less than 175 days because potential vascular dysfunction is exacerbated by the circulatory demands of pregnancy. Wistar rats were fed an isocaloric diet containing either 18% (control group) or 9% (low-protein group) casein throughout pregnancy. The female offspring were fed standard chow and mated between days 70 and 125. At the end of pregnancy, blood pressure was measured, and the uterine arteries were dissected and investigated with a wire myograph. Placental weights were significantly lower in offspring of the low-protein group versus control. There were no significant differences in blood pressure. Renal expression of AT1 receptor mRNA was greater, and of AT2 receptor was less, in the low-protein group versus control. Vasoconstriction of uterine arteries to phenylephrine and U46619 was increased in the low-protein group, and vasodilatation to sodium nitroprusside was also increased. Low-protein diet induces vascular effects on female offspring in their pregnancy, in terms of increased uterine artery vasoconstriction. This may be compensated for by increased sensitivity to nitric oxide (NO), maintaining blood pressure normal in the face of the demands of pregnancy. Such renal and vascular effects, combined with placental size, may transmit risk of vascular dysfunction to subsequent generations.
    No preview · Article · Apr 2011 · Journal of Obstetrics and Gynaecology Research
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    ABSTRACT: 背景: 妊娠中の母体の低蛋白栄養により, 児の成人期での高血圧, 冠血管障害, 糖尿病などの成人病が発症しやすくなることが知られている. さらに動物実験では雌より雄に高血圧が発症しやすくなることが明らかになっている. 過去にわれわれは卵巣を摘出し, 低エストロゲン状態にした母体低蛋白栄養のラットを用いた実験で, コントロール群に比べ, 母体低蛋白栄養群では高血圧や冠動脈周囲の線維化が有意に進行し, 卵巣摘出群でさらに顕著であることを証明している. また, wire myographを用いた血管機能評価では, ブラジキニンに対する血管拡張反応が有意に障害されたことから, 母体低蛋白栄養による高血圧や冠動脈血管周囲の線維化にはブラジキニンが関与していることも明らかにしてきた. そこで, 今回の実験は妊娠中の母体低蛋白栄養によるfetal programmingにより誘導された血管内皮細胞機 能障害がエストロゲン補充により改善することを研究仮説として実験を行った. 方法: Wistar ratを交配し, 妊娠中2つの栄養群;コントロール群 (C), 低蛋白栄養群 (R) に分け飼育した. 分娩後, 両群とも通常餌とし, 仔は日齢50に各群に対し次の3種の手術を行い, 合計6群を作成した;sham手術群 (CO, RO), 卵巣摘出群 (CX, RX), エストロゲン補充群 (CE, RE). 日齢50,100,150,175に血圧を測定し, 日齢175に腸間膜動脈を摘出しwire myographを用いて血管機能評価を行った. 結果: 血圧の変化はいずれの日齢においても各群間に有意差を認めなかった. wire myographにおいては, ブラジキニンに対する血管拡張反応がCOに対しRO, RXで有意に鈍化し, REで有意に改善を認めた. 結論: 母体低蛋白栄養で起こる血管機能障害における性差発現にはエストロゲンが関与していることが再確認された. また, 引き起こされた血管機能障害はエストロゲンを補充することで代償することができる可能性があることが示唆された.
    No preview · Article · Jan 2011
  • M. Miyakawa · Y. Musha · M. Ohtsuji · S. Itoh · S. Takeda

    No preview · Article · Sep 2007 · Early Human Development