| Project/Area Number |
16591679
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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 | Nagoya City University |
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Principal Investigator |
SUZUKI Yoshikatsu Nagoya City University, Graduate School of Medical Sciences, Associate Professor, 大学院・医学研究科, 助教授 (30254288)
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| Co-Investigator(Kenkyū-buntansha) |
ITOH Takeo Nagoya City University, Graduate School of Medical Sciences, Professor, 大学院・医学研究科, 教授 (70159888)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Preeclampsia / endothelial dysfunction / folic acid / L-arginine / animal models / 妊娠高血圧症症候群 / ニトログリセリン / 妊娠中毒症 / アンギオテンシンII 1型受容体 |
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| Research Abstract |
Preeclampsia is characterized as increase in vascular resistance and permeability, and the disorder of blood coagulation. Its pathophysiology might involve the dysfunction of endothelium-derived relaxing factors, such as nitric oxide (NO), prostacyclin and endothelium-derived hyperpolarizing factor (EDHF). It was found that the activity of NO and prostacyclin (not but EDHF) might be reduced in omental resistance artery obtained from preeclamptic women. On further investigation, the reduced activity of NO might be mainly caused by impaired action of cGMP (the second messenger of NO), while reduced action of prostacyclin might be caused by decrease in its production. However, EDHF might be preserved, suggesting that it might be compensate for these disorders. From these results the endothelial dysfunction seen in preeclampsia, which is so called "endothelial cell activation" might be specific (since it is different from endothelial dysfunction in other pathological state, such as hyperte
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nsion and diabetes).
What causes "endothelial cell activation" and develops preeclampsia? We investigated whether or not superoxide generation cause to reduce the endothelial cell function in animal models. The reduced action of endothelial NO as well as NO donor and cGMP analogue was seen in mesenteric artery obtained from nitroglycerin (NTG)-treated rabbit. The reduction might be dependent on superoxide generation by activated angiotensin II type 1 receptor. Furthermore, it was suggested that endothelial NO synthase (eNOS) uncoupling might occur in resistance artery of NTG rabbit, since L-arginine plus 5-methyltetrahydrofolate (activated folic acid) could improve the reduction.
In preliminary study, an oral supplementation of L-arginine plus folic acid also might recover the reduced endothelial function in high risk pregnant women using flow-mediated vasodilatation of brachial artery by reactive hyperemia.
From these results, it was suggested that the administration of L-arginine plus folic acid might improve the endothelial dysfunction by possibly blocking eNOS uncoupling in women complicated with preeclampsia. Less
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