Effect of stretch on the intracellular Ca2+-dependent spontaneous activity of pulmonary vein myocardium
Project/Area Number |
17K15460
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Pharmacology in pharmacy
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Research Institution | Toho University |
Principal Investigator |
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | 肺静脈心筋 / 自発活動 / 心房細動 / angiotensinⅡ / 伸展負荷 / AngiotensinⅡ / 薬理学 |
Outline of Final Research Achievements |
We examined the effects of stretch and angiotensin II on electrical spontaneous activity of pulmonary vein myocardium, which can be a risk factor for atrial fibrillation. In guinea pig isolated pulmonary vein tissue preparations, angiotensin II induced electrical spontaneous activity, which was suppressed by losartan (AT1 receptor antagonist), xestospongin C (IP3 receptor inhibitor) and SEA0400 (Na+/Ca2+ exchanger inhibitor). These results indicated that angiotensin II promotes the Ca2+ release from IP3 receptor via the AT1 receptor, which triggers the generation of electrical spontaneous activity of pulmonary vein myocardium by Na+/Ca2+ exchanger.
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Academic Significance and Societal Importance of the Research Achievements |
心房細動は臨床で最も多く見られる不整脈の一つである。患者数が多く(日本に130万人)、心原性脳梗塞を誘発するなど患者のQOLを損なうことから、治療意義の大きい疾患と考えられているが、有効かつ安全な治療薬は未だ存在しない。近年、心房細動の原因の大半が左心房に隣接する肺静脈内に局在する心筋組織の異所性自動能であることが判明した。また高血圧症や心不全などの心房細動の危険因子の多くは肺静脈に持続的な負荷がかかるものである。従ってこの肺静脈自動能が引き起こされる機序を解明し、それを抑制する薬物を見出すことができれば、心房細動の新たな治療戦略の開発に繋がると考えられる。
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Report
(4 results)
Research Products
(64 results)
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[Journal Article] Cardiac overexpression of Epac1 in transgenic mice rescues lipopolysaccharide-induced cardiac dysfunction and inhibits Jak-STAT pathway.2017
Author(s)
Huiling Jin, Takayuki Fujita, Meihua Jin, Reiko Kurotani, Iyuki Namekata, Shogo Hamaguchi, Yuko Hidaka, Wenqian Cai, Kenji Suita, Yoshiki Ohnuki, Yasumasa Mototani, Kouichi Shiozawa, Rajesh Prajapati, Chen Liang, Masanari Umemura, Utako Yokoyama, Motohiko Sato, Hikaru Tanaka, Satoshi Okumura, Yoshihiro Ishikawa.
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Journal Title
J Mol Cell Cardiol.
Volume: 108
Pages: 170-180
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Haruna Kanae, Shogo Hamaguchi, Yumi Wakasugi, Taichi Kusakabe, Keisuke Kato, Iyuki Namekata, Hikaru Tanaka. Pathological prolongation of action potential duration as a cause of the reduced alpha-adrenoceptor-mediated negative inotropy in streptozotocin-induced diabetic mice myocardium.2017
Author(s)
Haruna Kanae, Shogo Hamaguchi, Yumi Wakasugi, Taichi Kusakabe, Keisuke Kato, Iyuki Namekata, Hikaru Tanaka.
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Journal Title
J Pharmacol Sci.
Volume: 135(3)
Issue: 3
Pages: 131-133
DOI
Related Report
Peer Reviewed / Open Access
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