| Project/Area Number |
10671560
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
OKAWA Toshiaki Fukushima Medical University, Sch. of Med., assistant, 医学部, 助手 (00254011)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | NO. / uterus / uterine contraction / NOx / K ca channel / NO denor / placento / preterm birth / 子宮筋 / NOドナー / ラット / Nitric Oxide (NO) / 妊娠 / 血清 / NO代謝産物 |
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| Research Abstract |
We demonstrated that an L-arginine-NO-cGMP pathway exists in pregnant rat uterus, through in vitro and in vivo experiments. Nitric oxide inhibits spontaneous contractions in rate uterus at midgestation but not at term, demonstrating gestational age-dependent inhibition. There is gestational age-dependent refractoriness to calcium-dependent potassium but not adenosine triphosphate-dependent potassium channel opener-induced inhibition of spontaneous contractile activity of isolated rat uterine rings. Nitric oxide inhibits uterine contractions by opening of calcium-dependent potassium channels in pregnant rat myometrium. Refractoriness to nitric oxide toward term may result from decreased probability to open or number of calcium-dependent potassium channels. The presence of placental tissue enhances inhibition of uterine contractility by agents that spontaneously release nitric oxide, such as diethylamine-nitric oxide, but no by nitroglycerin, which requires metabolic transformation for nitric oxide to be released. Refractoriness to nitric oxide near or at term does not depend on the presence or absence of placental tissue.
The plasma NO metabolite concentration in 22-26 weeks of pregnancy was significantly higher than that of the non-pregnant women, although the plasma NO metabolite concentration was slightly decreased toward term. The plasma NO metabolite concentration in patients with preterm labor was lower than that of the normal pregnant women in same weeks of pregnancy. Therefore, decreasing NO products may be one of the causes of preterm birth.
These studies suggest that NO has an important role in maintaining uterine quiescence at midgestation. A decrease in uterine relaxation responsiveness to NO at term may play a role in the initiation of labor. Nitric oxide donor drugs may be very effective in suppressing preterm labor.
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