Studies for Mechanisms of Fetal Placental Insufficiency Using Dually Perfused Human Placenta
| Project/Area Number |
12671638
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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 | Aichi Medical University |
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Principal Investigator |
ASAI Mitsuoki (2001-2002) Aichi Medical University, Department of Obstetrics and Gynecology, Associate Professor, 医学部, 助教授 (50151014)
鈴木 正利 (2000) 愛知医科大学, 医学部, 助教授 (90093426)
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| Co-Investigator(Kenkyū-buntansha) |
HOJO Keiko Aichi Medical University, Department of Obstetrics and Gynecology, Assistant Professor, 医学部, 助手 (30288534)
浅井 光興 愛知医科大学, 医学部, 助教授 (50151014)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Human Placenta / Chorionic Plate Vessel / Placental perfusion / ADMA / Serotonin / Ethanol / NO / L-NAME / 胎盤胎児側循環 / 胎盤灌流 / indomethacin / prostacyclin / tetrahydrobiopterin / asymmetrical dimethylarginine / endothelin-1 / serotonin / 血管リング |
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| Research Abstract |
The aim of this study was to investigate the effects of various vasoactive factors on the human fetal placental vessels and to elucidate their mechanisms of actions using dually perfused placenta in vitro.
At first, we studied the effect of ethanol on placental circulation, and the acting mechanisms for this using a ring model of human fetal-placental vessels. This study demonstrates that ethanol acts to constrict vessels and raise the perfusion pressure on the fetal side of human placental circulation. These results show that the mechanism for this vessel-constricting action is related to a Ca^<2+> channel agonist-like activity, and the release of Ca^<2+> from the endoplasmic reticulum. In experiments using placental perfusion, the pre-administration of NG-nitro-L-arginine metyl ester-2HCl (L-NAME) intensified the vasopressor response to ethanol, while indomethacin (INDO) weakened it. However, in the experiment using isolated placental vessel rings, the pre-administration of L-NAME or
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INDO had no effect on the ethanol induced constriction. These results show that the NO produced by placental tissue suppresses the vessel-constricting response brought about by ethanol, whereas PGs intensify it. In conclusion, it appears that in the mechanism for fetal alcohol syndrome, which represents developmental delays in the intrauterine fetus, the impaired placental circulation due to the vessel-constricting action of ethanol is clearly involved.
Nitric oxide has a very important role in pre-eclampsia. We elucidated that; 1) Preincubation with indomethacin or L-NAME potentiated the contraction response to ET-1 and 5-HT, and both maximum tension and sensitivity were significantly increased under the conditions in 5-HT, and with L-NAME. That sensitivity was almost equal as ET-1, which is a potent vasoconstrictor. 2) The blood concentration of 5-HT was significantly higher than ET-1. These results suggested that 5-HT under the condition of NO synthase insufficiency (pre-eclampsia) was most potent vasoconstrictor. 3) Asymmetric dimethylarginine (ADMA) is well known as a natural inhibitor for NO synthase, and the blood concentration of ADMA was significantly higher in pre-eclamptic patients, and remarkably high in fetal circulation than in maternal circulation. These results hypothesize that the most potent factor for the elevation of blood pressure and intra-uterine growth retardation (IUGR) may be ADMA.
We need more effort to elucidate the mechanisms of actions of other vasoactive factors in human fetal placental vessels and the interaction of these factors. If these mechanisms were elucidated, we could show the mechanisms of IUGR because of the impairment of fetal placental circulation, and also show the therapeutical way for IUGR. Less
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Report
(4 results)
Research Products
(6 results)
