{"created":"2022-02-24T07:47:58.959103+00:00","id":2017764,"links":{},"metadata":{"_buckets":{"deposit":"304c6070-c005-46cd-90a2-220c5b38f301"},"_deposit":{"id":"2017764","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"2017764"},"status":"published"},"_oai":{"id":"oai:u-ryukyu.repo.nii.ac.jp:02017764","sets":["1642838163960:1642838198944:1642838199408:1642838228645","1642838403551:1642838412624"]},"author_link":[],"item_1617186331708":{"attribute_name":"Title","attribute_value_mlt":[{"subitem_1551255647225":"[総説]Dihydrobiopterin による内皮型一酸化窒素合成酵素機能障害","subitem_1551255648112":"ja"},{"subitem_1551255647225":"[REVIEW]Impairment by dihydrobiopterin of endothelial nitric oxide function in vivo","subitem_1551255648112":"en"}]},"item_1617186419668":{"attribute_name":"Creator","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"野口, 克彦","creatorNameLang":"ja"}]},{"creatorNames":[{"creatorName":"濱舘, 直史","creatorNameLang":"ja"}]},{"creatorNames":[{"creatorName":"松﨑, 俊博","creatorNameLang":"ja"}]},{"creatorNames":[{"creatorName":"坂梨, まゆ子","creatorNameLang":"ja"}]},{"creatorNames":[{"creatorName":"仲宗根, 淳子","creatorNameLang":"ja"}]},{"creatorNames":[{"creatorName":"内田, 太郎","creatorNameLang":"ja"}]},{"creatorNames":[{"creatorName":"新垣, 久美子","creatorNameLang":"ja"}]},{"creatorNames":[{"creatorName":"久保田, 陽秋","creatorNameLang":"ja"}]},{"creatorNames":[{"creatorName":"石内, 勝吾","creatorNameLang":"ja"}]},{"creatorNames":[{"creatorName":"益崎, 裕章","creatorNameLang":"ja"}]},{"creatorNames":[{"creatorName":"須加原, 一博","creatorNameLang":"ja"}]},{"creatorNames":[{"creatorName":"大屋, 祐輔","creatorNameLang":"ja"}]},{"creatorNames":[{"creatorName":"坂梨, 又郎","creatorNameLang":"ja"}]},{"creatorNames":[{"creatorName":"筒井, 正人","creatorNameLang":"ja"}]},{"creatorNames":[{"creatorName":"Noguchi, Katsuhiko","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"Hamadate, Naobumi / 浜館, 直史 / 濱館, 直史 / 浜舘, 直史","creatorNameLang":"ja"}]},{"creatorNames":[{"creatorName":"Matsuzaki, Toshihiro / 松崎, 俊博","creatorNameLang":"ja"}]},{"creatorNames":[{"creatorName":"Sakanashi, Mayuko","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"Nakasone, Junko","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"Uchida, Taro","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"Arakaki, Kumiko","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"Kubota, Haruaki","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"Ishiuchi, Shogo","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"Masuzaki, Hiroaki","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"Sugahara, Kazuhiro","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"Ohya, Yusuke","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"Sakanashi, Matao","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"Tsutsui, Masato","creatorNameLang":"en"}]}]},"item_1617186476635":{"attribute_name":"Access Rights","attribute_value_mlt":[{"subitem_1522299639480":"open access","subitem_1600958577026":"http://purl.org/coar/access_right/c_abf2"}]},"item_1617186499011":{"attribute_name":"Rights","attribute_value_mlt":[{"subitem_1522650717957":"ja","subitem_1522651041219":"琉球医学会"}]},"item_1617186626617":{"attribute_name":"Description","attribute_value_mlt":[{"subitem_description":"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.","subitem_description_type":"Other"},{"subitem_description":"論文","subitem_description_type":"Other"}]},"item_1617186643794":{"attribute_name":"Publisher","attribute_value_mlt":[{"subitem_1522300295150":"ja","subitem_1522300316516":"琉球医学会"}]},"item_1617186702042":{"attribute_name":"Language","attribute_value_mlt":[{"subitem_1551255818386":"jpn"}]},"item_1617186920753":{"attribute_name":"Source Identifier","attribute_value_mlt":[{"subitem_1522646500366":"ISSN","subitem_1522646572813":"1346-888X"},{"subitem_1522646500366":"NCID","subitem_1522646572813":"AN10369445"}]},"item_1617186941041":{"attribute_name":"Source Title","attribute_value_mlt":[{"subitem_1522650068558":"ja","subitem_1522650091861":"琉球医学会誌 = Ryukyu Medical Journal"}]},"item_1617187056579":{"attribute_name":"Bibliographic Information","attribute_value_mlt":[{"bibliographicIssueNumber":"1･2","bibliographicPageEnd":"12","bibliographicPageStart":"7","bibliographicVolumeNumber":"32"}]},"item_1617258105262":{"attribute_name":"Resource Type","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_1617265215918":{"attribute_name":"Version Type","attribute_value_mlt":[{"subitem_1522305645492":"VoR","subitem_1600292170262":"http://purl.org/coar/version/c_970fb48d4fbd8a85"}]},"item_1617605131499":{"attribute_name":"File","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_access","filename":"v3212p7.pdf","mimetype":"application/pdf","url":{"objectType":"fulltext","url":"https://u-ryukyu.repo.nii.ac.jp/record/2017764/files/v3212p7.pdf"},"version_id":"c9d86f2c-1ed3-4f7b-9102-8957c2ffa5b6"}]},"item_title":"[総説]Dihydrobiopterin による内皮型一酸化窒素合成酵素機能障害","item_type_id":"15","owner":"1","path":["1642838228645","1642838412624"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2015-04-24"},"publish_date":"2015-04-24","publish_status":"0","recid":"2017764","relation_version_is_last":true,"title":["[総説]Dihydrobiopterin による内皮型一酸化窒素合成酵素機能障害"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2022-02-24T07:48:02.495089+00:00"}