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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/2711

Title: Oral administration of a novel long-acting prostacyclin agonist with thromboxane synthase inhibitory activity for pulmonary arterial hypertension.
Other Titles: 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
Authors: Nakamura, Atsuhiro
Nagaya, Noritoshi
Obata, Hiroaki
Sakai, Katsuya
Sakai, Yoshiki
Yoshikawa, Masanori
Hamada, Kaoru
Matsumoto, Kunio
Kimura, Hiroshi
Keywords: cAMP
Hepatocyte growth factor
Monocrotaline
Pulmonary arterial hypertension
Thromboxane synthase
Issue Date: Aug-2013
Publisher: 日本循環器学会 / Japanese Circulation Society
Citation: Circulation journal Vol.77 No.8 p.2127-2133
Abstract: 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.
Description: 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/
URI: http://hdl.handle.net/10564/2711
ISSN: 13469843
DOI: http://dx.doi.org/10.1253/circj.CJ-13-0107
Academic Degrees and number: 24601B1326
Degree-granting date: 2014-03-17
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2013年度

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