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

• Material Type: 博士論文
• Title: Oral administration of a novel long-acting prostacyclin agonist with thromboxane synthase inhibitory activity for pulmonary arterial hypertension.
• Author/Editor: Nakamura, Atsuhiro; Nagaya, Noritoshi; Obata, Hiroaki; Sakai, Katsuya; Sakai, Yoshiki; Yoshikawa, Masanori; Hamada, Kaoru; Matsumoto, Kunio; Kimura, Hiroshi
• Author Heading: Nakamura, Atsuhiro; Nagaya, Noritoshi; Obata, Hiroaki; Sakai, Katsuya; Sakai, Yoshiki; Yoshikawa, Masanori; Hamada, Kaoru; Matsumoto, Kunio; Kimura, Hiroshi
• Publication, Distribution, etc.: 日本循環器学会 / Japanese Circulation Society
• Publication Date: 2013-08
• Publication Date (W3CDTF): 2013-08
• Alternative Title: 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
• Periodical title: Circulation journal
• No. or year of volume/issue: 77 8
• Volume: 77
• Issue: 8
• Pages: 2127-2133
• ISSN (Periodical Title): ISSN : 1346-9843
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2014-03-17
• Dissertation Number: 乙第1326号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: cAMP; Hepatocyte growth factor; Monocrotaline; Pulmonary arterial hypertension; Thromboxane synthase
• Target Audience: 一般
• Note (General): 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
• Source: fulltext; 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; 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; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2711/6/03%e6%9c%ac%e6%96%87.pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1253/circj.CJ-13-0107
• Periodical Title (NCID): AA11591968; https://ci.nii.ac.jp/ncid/AA11591968
• Data Provider (Database): 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
• Original Data Provider (Database): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU