Item type |
デフォルトアイテムタイプ(フル)(1) |
公開日 |
2015-04-24 |
タイトル |
|
|
タイトル |
[総説]Dihydrobiopterin による内皮型一酸化窒素合成酵素機能障害 |
|
言語 |
ja |
タイトル |
|
|
タイトル |
[REVIEW]Impairment by dihydrobiopterin of endothelial nitric oxide function in vivo |
|
言語 |
en |
作成者 |
野口, 克彦
濱舘, 直史
松﨑, 俊博
坂梨, まゆ子
仲宗根, 淳子
内田, 太郎
新垣, 久美子
久保田, 陽秋
石内, 勝吾
益崎, 裕章
須加原, 一博
大屋, 祐輔
坂梨, 又郎
筒井, 正人
Noguchi, Katsuhiko
Hamadate, Naobumi / 浜館, 直史 / 濱館, 直史 / 浜舘, 直史
Matsuzaki, Toshihiro / 松崎, 俊博
Sakanashi, Mayuko
Nakasone, Junko
Uchida, Taro
Arakaki, Kumiko
Kubota, Haruaki
Ishiuchi, Shogo
Masuzaki, Hiroaki
Sugahara, Kazuhiro
Ohya, Yusuke
Sakanashi, Matao
Tsutsui, Masato
|
アクセス権 |
|
|
アクセス権 |
open access |
|
アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
権利情報 |
|
|
言語 |
ja |
|
権利情報 |
琉球医学会 |
内容記述 |
|
|
内容記述タイプ |
Other |
|
内容記述 |
Dihydrobiopterin (BH2), an oxidized form of tetrahydrobiopterin (BH4) which is an essential cofactor of nitric oxide synthase, has been reported to be elevated in association with oxidative stress-related cardiovascular disorders such as hypertension and diabetes. However, the role of BH2 in the regulation of endothelial nitric oxide synthase (eNOS) activity in vivo remains unknown. Thus, we aimed to clarify whether increasing intracellular BH2 levels causes eNOS dysfunction in rats. The BH2 precursor sepiapterin (SEP) was intravenously given after administration of the specific dihydrofolate reductase inhibitor methotrexate (MTX) to block intracellular conversion of BH2 to BH4. MTX/SEP treatment markedly augmented aortic BH2 levels by 8.7- fold but did not affect aortic BH4 levels compared with control (saline) treatment. MTX alone did not significantly alter BH4 or BH2 levels. MTX/SEP, but not MTX alone, impaired vasodilator responses induced by acetylcholine (ACh), an endotheliumdependent vasodilator, and also attenuated ACh-induced relaxations of isolated aortas, indicating impairment of endothelial function. Importantly, MTX/SEP treatment significantly enhanced NOS inhibitor-sensitive superoxide production, suggesting the involvement of eNOS uncoupling. MTX/SEP treatment modified the eNOS phosphorylation state into a reduced eNOS activity. The present data indicate that BH2, even in the absence of BH4 deficiency, causes impairment of eNOS function in vivo, and suggest a novel role of BH2 in endothelial dysfunction. |
内容記述 |
|
|
内容記述タイプ |
Other |
|
内容記述 |
論文 |
出版者 |
|
|
言語 |
ja |
|
出版者 |
琉球医学会 |
言語 |
|
|
言語 |
jpn |
資源タイプ |
|
|
資源タイプ |
journal article |
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
収録物識別子 |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
1346-888X |
収録物識別子 |
|
|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AN10369445 |
収録物名 |
|
|
言語 |
ja |
|
収録物名 |
琉球医学会誌 = Ryukyu Medical Journal |
書誌情報 |
巻 32,
号 1・2,
p. 7-12
|