2004 Fiscal Year Final Research Report Summary
The role of nitric oxide on the vascular tone of the ductus arteriosus
| Project/Area Number |
14570715
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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 |
Pediatrics
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
KAJINO Hiroki Asahikawa Medical College, School of Medicine, pediatrics, instructor, 医学部, 講師 (70292109)
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| Co-Investigator(Kenkyū-buntansha) |
TSUDA Naoya Asahikawa Medical College, School of Medicine, pediatrics, senior staff, 医学部, 助手 (10302001)
FUJIEDA Kenji Asahikawa Medical College, School of Medicine, pediatrics, professor, 医学部, 教授 (60173407)
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| Project Period (FY) |
2002 – 2004
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| Keywords | ductus arteriosus / nitric oxide / estrogen / gene polymorphism / nitric oxide synthase / patent ductus arteriosus in premature infants / international cooperation on science / United States of America |
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| Research Abstract |
Nitric oxide plays a significant role in vascular tone of the ductus arteriosus as well as prostaglandins. The purpose of this study is to seek factors that regulate nitric oxide production in the ductus arteriosus, leading to facilitate controlling the vascular tone of the ductus and ultimately to improve prognosis of the infants with heart diseases, such as patent ductus arteriosus and ductus-dependent circulation.
1.Hypothesis-1
It is known that estrogen augments nitric oxide production in vasculature. The first hypothesis is "high blood level of estrogen during fetal life contributes to potency of the ductus. Withdrawal of the estrogen level after birth contributes to closure of the ductus".
In vivo study : we administered estrogen receptor blockers-tamoxifen and ICI 182780, cyclooxygenase inhibitor-indomethacin, and nitric oxide synthase inhibitor-L-NAME to pregnant rats and measured diameters of the ductus and main pulmonary artery of the fetus. Although indomethacin and L-NAME sign
… More
ificantly decreased the ductus : pulmonary artery diameter ratio, either tamoxifen or ICI 182780 did not. It suggests that estrogen might not have a significant impact on nitric oxide production in the fetal ductus.
In vitro study : we tried to measure isometric tension of the ductus ring excised from the fetal rats under the drugs described above. However, we could not obtain informative data.
2.Hypothesis-2
Indomethacin is a potent constrictor of the ductus, so that we administer it to premature infants who suffer from patent ductus arteriosus. However, some infants respond to indomethacin and others do not. Thus, we consider that it might be attributed to nitric oxide production in the ductus. The second hypothesis is "the pattern of polymorphism of nitric oxide synthase gene in premature infants with patent ductus arteriosus differs between in those who respond to indomethacin and in those who do not".
So far, the pattern of 894G/T ; Glu296Asp in exon 7, one of the ecNOS gene polymorphism, did not statistically differ between the two groups. A large number of the premature infant might reveal statistical significance.
We co-operated with Dr.RI Clyman, a professor of UCSF, USA, to perform this study, accomplishing several scientific papers below. Less
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Research Products
(10 results)
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[Journal Article] Prostaglandin E2--mediated relaxation of the ductus arteriosus : effects of gestational age on g proteincoupled receptor expression, signaling, and vasomotor control.2004
Author(s)
Waleh N^*, Kajino H^*, Marrache AM, Ginzinger D, Roman C, Seidner SR, Moss TI, Fouron JC, Vazquez-Tello A, Chemtob S, Clyman RI.(^*Both authors have equally contributed to the submitted work.)
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Journal Title
Circulation. 110(16)
Pages: 2326-2332
Description
「研究成果報告書概要(欧文)」より
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