| Project/Area Number |
10671558
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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 | Kumamoto University |
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Principal Investigator |
TOSHIMURA Toshihiro Kumamoto University, University Hospital, Lecturer, 医学部・附属病院, 講師 (70220738)
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| Co-Investigator(Kenkyū-buntansha) |
OKAMURA Hitoshi Kumamoto University, School of Medicine, Professor, 医学部, 教授 (20026983)
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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 |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | nitric oxide / NィイD1GィエD1-monomethyl-L-arginine / angiotensin II / Rat / endothelial nitric oxide synthase / preeclampsia / genetics / polymorphism / 一酸化窒素 / 高血圧 / N-NMMA / アンギオテンシンII / アルギニン |
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| Research Abstract |
Study 1 : Animal experiment ;
To investigate the mechanism of attenuated pressor responses to several vasoconstrictors during gestation, we sought to characterize the effects of NィイD1GィエD1-monomethyl-L-arginine (L-NMMA) and L-arginine (L-Arg) on the pressor response to the infusion of angiotensin II in rats. L-NMMA and L-Arg were infused intraperitoneally into rats at a constant rate by means of an osmotic minipump. The animals were anesthetized on day 13, and catheters were placed into the femoral artery and vein. After the animals had recovered from the anesthesia, the pressor response to intravenous bolus doses of angiotensin II were determined after recovery from anesthesia. The pressor response to angiotensin II in the L-NMMA group was significantly increased as compared with that in the control group. The response of the L-NMMA plus L-Arg group did not differ significantly from that of the control group. Results indicate that the infusion of a nitric oxide synthase inhibitor, at a
… More
dose insufficient to produce hypertension increases the pressor response to angiotensin II.
Study 2 : Molecular genetics of preeclampsia patients ;
We recently identified a variant within exon 7 of the endothelial nitric oxide synthase (eNOS) gene : G to T conversion at nucleotide position 894 resulting in replacement of glutamic acid with aspartic acid at codon 298 (Glu298Asp). We analyzed the association between the Glu298Asp eNOS gene variant and preeclampsia. The study included 152 preeclampsia patients (35 mild, 80 severe and 37 superimposed) and 170 control subjects. Screening for the Glu298Asp eNOS gene variant was carried out by analysis of polymerase chain reaction-restriction fragment length polymorphism. The frequency of the Glu298Asp variant was significantly higher in the severe preeclampsia group (28.8%) than in the control (14.1% ; p<0.01), superimposed preeclampsia (8.1% ; p<0.01) or mild preeclampsia (11.4% ; p<0.01) groups. We conclude that the presence of the Glu298Asp eNOS gene could be a marker of increased risk of developing preeclampsia. Less
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