Oral administration of a novel long-acting prostacyclin agonist with thromboxane synthase inhibitory activity for pulmonary arterial hypertension.

• 資料種別: 博士論文
• タイトル: Oral administration of a novel long-acting prostacyclin agonist with thromboxane synthase inhibitory activity for pulmonary arterial hypertension.
• 著者・編者: Nakamura, Atsuhiro; Nagaya, Noritoshi; Obata, Hiroaki; Sakai, Katsuya; Sakai, Yoshiki; Yoshikawa, Masanori; Hamada, Kaoru; Matsumoto, Kunio; Kimura, Hiroshi
• 著者標目: Nakamura, Atsuhiro; Nagaya, Noritoshi; Obata, Hiroaki; Sakai, Katsuya; Sakai, Yoshiki; Yoshikawa, Masanori; Hamada, Kaoru; Matsumoto, Kunio; Kimura, Hiroshi
• 出版事項: 日本循環器学会 / Japanese Circulation Society
• 出版年月日等: 2013-08
• 出版年（W3CDTF）: 2013-08
• 並列タイトル等: 肺高血圧症に対するトロンボキサン合成阻害作用をもった新規長期作用型プロスタサイクリンアゴニストの経口投与
• タイトル（掲載誌）: Circulation journal
• 巻号年月日等（掲載誌）: 77 8
• 掲載巻: 77
• 掲載号: 8
• 掲載ページ: 2127-2133
• ISSN（掲載誌）: ISSN : 1346-9843
• 授与機関名: 奈良県立医科大学
• 授与年月日: 2014-03-17
• 報告番号: 乙第1326号
• 学位: 博士（医学）
• 本文の言語コード: eng
• 件名標目: cAMP; Hepatocyte growth factor; Monocrotaline; Pulmonary arterial hypertension; Thromboxane synthase
• 対象利用者: 一般
• 一般注記: type:Thesis; BACKGROUND: Continuous administration of prostacyclin has improved the survival of patients with pulmonary arterial hypertension (PAH). However, this treatment has some problems, including its short duration of activity and difficult delivery. Therefore, we developed ONO-1301, an orally active, long-acting prostacyclin agonist with thromboxane synthase inhibitory activity. METHODS AND RESULTS: We investigated whether oral administration of ONO-1301 can both prevent and reverse monocrotaline (MCT)-induced PAH in rats. Rats were randomly assigned to receive repeated oral administration of ONO-1301 twice daily beginning either 1 or 8 days after subcutaneous injection of MCT. A control group received oral saline, and a sham group received a subcutaneous injection of saline instead of MCT. MCT-treated controls developed significant pulmonary hypertension. Treatment with ONO-1301 from day 1 or 8 significantly attenuated the increases in right ventricular systolic pressure and the increase in medial wall thickness of pulmonary arterioles. Kaplan-Meier survival curves demonstrated that the effect of ONO-1301 was equivalent to that of an endothelin receptor antagonist and a phosphodiesterase-5 inhibitor. A single oral dose of ONO-1301 increased plasma cAMP levels for up to 6h. Treatment with ONO-1301 significantly decreased urinary 11-dehydro-thromboxane B2 and increased the plasma hepatocyte growth factor concentration. CONCLUSIONS: Oral administration of ONO-1301 ameliorated PAH in rats, an effect that may occur through cAMP and hepatocyte growth factor.; 博士（医学）・乙1326号・平成26年3月17日; 日本循環器学会の許諾を得て登録（2014年6月6日付）; ジャーナル公式サイト（日本循環器学会HP内）：https://www.j-circ.or.jp/journal/; 公開サイト（J-STAGE）：https://www.jstage.jst.go.jp/browse/circj/; identifier:Circulation journal Vol.77 No.8 p.2127-2133; identifier:13469843; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2711; identifier:Circulation journal, 77(8): 2127-2133
• オンライン閲覧公開範囲: インターネット公開
• 関連情報（DOI）: 10.1253/circj.CJ-13-0107
• 連携機関・データベース: 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• 提供元機関・データベース: 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU

目次

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2711/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2711/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2711/6/03%e6%9c%ac%e6%96%87.pdf fulltext