Studies for Mechanisms of Actions of Vasoactive Factors in Human Placental Vessels

人胎盘血管活性因子作用机制的研究

• 批准号: 07671833
• 负责人: SUZUKI Masatoshi
• 金额: $ 1.28万
• 依托单位: Aichi Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671833/
• 关键词: Human Placenta; Chorionic Plate Vessel; Nitric Oxide; Endothelin; Serotonin; Ethanol; Estrogen; L-NAME; ニトロプルシッド; ベラパミル; イオンチャンネル; カフェイン; EDHF; U-46619; L-Arginine

The aim of this study was to investigate the effects of various vasoactive factors on the human placental vessels and to elucidate their mechanisms of actions.We could show that ; 1) endothelin-1 (ET-1), U-46619 and serotonin (5-HT) produced concentration-dependent contractions in placental vessels, but angiotensin II and phenylephrine demonstrated no constrictor activity, 2) a subthreshold concentration of ET-1 potentiated significantly the contractile response and sensitivity of 5-HT,3) preincubation in indomethacin and L-NAME potentiated the contraction response to ET-1 and 5-HT,and especially in 5-HT both maximum tension and sensitivity were significantly increased, 4) estradiol (E2) revealed a vasodilated activity antagonized to tamoxifen in fetal placental circulation, 5) the mechanisms of vasodilated activity of E2 were stimulation of cyclooxygenase activity, rapid antagonism of calcium channel, and agonistic function to potassium channel, 6) vasoconstrictor effect of ethanol was revealed in both placental perfusion study and vessel ring study, and 7) vasoconstricted activities of ethanol were induced by the influx of extracellular calcium and the release of calcium from the intracellular calcium store.We need more effort to elucidate the mechanisms of actions of other vasoactive factors in human placental vessels and the interaction of these factors. If these studies were completed, we could show the mechanisms of intra-uterine growth retardation (IUGR) because of the impairment of placental circulation, and also show the therapeutical way for IUGR.

本研究的目的是探讨各种血管活性因子对人胎盘血管的作用，并阐明其作用机制。（1）内皮素-1（ET-1）、U-46619和5-羟色胺（5-HT）对胎盘血管产生浓度依赖性收缩作用，而血管紧张素II和苯肾上腺素无收缩作用;（2）阈下浓度的ET-1可显著增强5-HT的收缩反应和敏感性;（3）吲哚美辛和L-NAME预孵育可增强ET-1和5-HT的收缩反应，其中尤以5-HT的最大张力和敏感性显著增加，4）雌二醇（E_2）对胎儿胎盘循环有舒张作用，可被三苯氧胺拮抗。5）E_2的舒张作用机制为：刺激环氧化酶活性，迅速拮抗钙通道，激动钾通道，6）胎盘灌流和血管环实验均显示乙醇的缩血管作用，和第7段）乙醇引起的血管收缩作用是通过细胞外钙内流和细胞内钙库释放钙引起的，其机制有待进一步阐明人类胎盘血管中其他血管活性因子的作用以及这些因子的相互作用。这些研究的完成，将有助于揭示胎盘循环障碍导致胎儿宫内发育迟缓（IUGR）的发病机制，并为IUGR的治疗提供新的思路。

项目成果

Mayumi Matsushita: "Effect of estradiol on fetal placental circulation in dually perfused human placenta" Journal of the Aichi Medical University Association. 26(1). 85-95 (1998)

Mayumi Matsushita：“雌二醇对双重灌注人胎盘中胎儿胎盘循环的影响”爱知医科大学协会杂志。

Keiko Maeda: "Amplifying factors of serotonin-induced vasoconstriction in human umbilical vessels" Journal of Japan Society for the Study of Toxemia of Pregnancy. 4. 131-132 (1996)

Keiko Maeda：“放大人脐血管中血清素诱导的血管收缩的因素”日本妊娠毒血症研究会杂志。

前田 佳子: "Serotoninによるヒト胎盤血管の収縮を増強する因子の検討" 日本妊娠中毒症学会雑誌. 4. 131-132 (1996)

Yoshiko Maeda：“增强血清素诱导的人胎盘血管收缩的因素的检查”日本先兆子痫学会杂志 4. 131-132 (1996)。

K.Sako: "Effect of ethanol on human placental vessels" Placenta. 18(8). A.12- (1997)

K.Sako：“乙醇对人类胎盘血管的影响”胎盘。

前田 佳子: "ヒト胎盤における血管作動性物質に対する反応の検討" 愛知医科大学医学会雑誌. 24. 59-70 (1996)

前田芳子：“人胎盘中血管活性物质的反应检查”爱知医科大学医学会杂志 24. 59-70 (1996)。