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著作: Kataoka Masaharu/Satoh Toru/Itoh Takefumi/Murakami Shinsuke/[岩瀬 俊]/Miyahara Yoshinori/Kyotani Shingo/Sakai Yoshiki/[寒川 賢治]/Ogawa Satoshi/A Long-Acting Prostacyclin Agonist with Thromboxane Inhibitory Activity for Pulmonary Hypertension/[American Journal of Respiratory and Critical Care Medicine]

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163888
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849202
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2017年3月6日(月) 13:35:11
Operator
三木 ちひろ
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[科長]/[徳島大学.病院.診療科.内科]
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種別 必須 学術論文(審査論文)
言語 必須 英語
招待 推奨
審査 推奨 Peer Review
カテゴリ 推奨 研究
共著種別 推奨
学究種別 推奨
組織 推奨
著者 必須
  1. (英) Kataoka Masaharu
    役割 任意
    貢献度 任意
    学籍番号 推奨
  2. (英) Satoh Toru
    役割 任意
    貢献度 任意
    学籍番号 推奨
  3. (英) Itoh Takefumi
    役割 任意
    貢献度 任意
    学籍番号 推奨
  4. (英) Murakami Shinsuke
    役割 任意
    貢献度 任意
    学籍番号 推奨
  5. 岩瀬 俊
    役割 任意
    貢献度 任意
    学籍番号 推奨
  6. (英) Miyahara Yoshinori
    役割 任意
    貢献度 任意
    学籍番号 推奨
  7. (英) Kyotani Shingo
    役割 任意
    貢献度 任意
    学籍番号 推奨
  8. (英) Sakai Yoshiki
    役割 任意
    貢献度 任意
    学籍番号 推奨
  9. 寒川 賢治(国立循環器病センター研究所)
    役割 任意
    貢献度 任意
    学籍番号 推奨
  10. (英) Ogawa Satoshi
    役割 任意
    貢献度 任意
    学籍番号 推奨
題名 必須

(英) A Long-Acting Prostacyclin Agonist with Thromboxane Inhibitory Activity for Pulmonary Hypertension

副題 任意
要約 任意

(英) Rationale: The balance between prostacyclin and thromboxane plays an important role in the regulation of pulmonary vascular tone. Recently, we developed ONO-1301, a novel, long-acting prostacyclin agonist with thromboxane synthase inhibitory activity. Objectives: We investigated whether modulation of prostacyclin/thromboxane balance by ONO-1301 ameliorates monocrotaline-induced pulmonary hypertension in rats. Methods: After subcutaneous injection of monocrotaline or vehicle, rats were randomized to receive repeated subcutaneous administration of ONO-1301 or vehicle twice per day for 3 wk. Measurements and Main Results: There was significant development of pulmonary hypertension 3 wk after monocrotaline injection. Treatment with ONO-1301 significantly attenuated the increases in right ventricular systolic pressure and ratio of right ventricular weight to body weight in monocrotaline rats. Furthermore, ONO-1301 significantly attenuated the increase in medial wall thickness of peripheral pulmonary arteries in monocrotaline rats. The half-life of plasma ONO-1301 concentration after a single subcutaneous administration was approximately 5.6 h. A single administration of ONO-1301 increased plasma cyclic adenosine 3', 5'-monophosphate level, which lasted at least up to 8 h. Treatment with ONO-1301 significantly decreased plasma 11-dehydro-thromboxane B2, a metabolite of thromboxane, in monocrotaline rats. Finally, Kaplan-Meier survival curves demonstrated that repeated administration of ONO-1301 improved survival rate in monocrotaline rats compared with vehicle administration (80 vs. 30% in 6-wk survival). Conclusions: Subcutaneous administration of a novel prostacyclin agonist (ONO-1301) markedly attenuated monocrotaline-induced pulmonary hypertension and improved survival in rats. The beneficial effects of ONO-1301 may occur through its long-lasting stimulation of cyclic adenosine 3', 5'-monophosphate and inhibition of thromboxane synthase.

キーワード 推奨
  1. (英) cAMP
  2. (英) monocrotaline
  3. (英) hemodynamics
  4. (英) vascular remodeling
発行所 推奨
誌名 必須 American Journal of Respiratory and Critical Care Medicine(American Thoracic Society/American Lung Association)
(pISSN: 1073-449X, eISSN: 1535-4970)
ISSN 任意 1073-449X
ISSN: 1073-449X (pISSN: 1073-449X, eISSN: 1535-4970)
Title: American journal of respiratory and critical care medicine
Title(ISO): Am J Respir Crit Care Med
Publisher: American Thoracic Society
 (NLM Catalog  (Scopus  (CrossRef (Scopus information is found. [need login])
必須 172
必須 12
必須 1575 1580
都市 任意
年月日 必須 2005年 12月 5日
URL 任意 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16192456
DOI 任意 10.1164/rccm.200501-102OC    (→Scopusで検索)
PMID 任意 16192456    (→Scopusで検索)
CRID 任意
WOS 任意 000234019000019
Scopus 任意 2-s2.0-30444453849
評価値 任意
被引用数 任意 1
指導教員 推奨
備考 任意
  1. (英) Article.Affiliation: Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.

  2. (英) Article.PublicationTypeList.PublicationType: Journal Article

  3. (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't