| Project/Area Number |
08670757
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | University of Tsukuba |
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Principal Investigator |
MIYAUCHI Takashi University of Tsukuba Institute of Clinical Medicine Assistant Professor, 臨床医学系, 講師 (60222329)
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| Co-Investigator(Kenkyū-buntansha) |
SAGISHITA Yasuro University of Tsukuba Institute of Clinical Medicine Professor, 臨床医学系, 教授 (90010131)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | endothelin / heart failure / molecular biology / endothelin antagonist / pathophysiology / cardiovascular pharmacology |
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| Research Abstract |
Cardiac myocytes and vascular endothelial cells produce endothelin (ET) -1, which increases the contractility of cardiac muscles and of vascular smooth muscles. ET-1 also exerts long-term effects such as myocardial hypertrophy, and causes cellular injury in cardiac myocytes. In the present work, we studied pathophysiological roles of ET-1 in heart failure using molecular biological, biochemical and pharmacological methods. Furthermore, we studied the effects of ET receptor antagonists on the animals with heart failure. In the case of heart failure, the production of ET-1 (both mRNA and peptide levels) was markedly increased in the failing heart and the long-term treatment with an ET receptor antagonist greatly improved the survival rate of rats with heart failure. This beneficial effect was accompanied by amelioration of cardiac dysfunction and amelioration of expression of cardiac genes of molecular markers (ANP mRNA,beta-myosin heavy chain mRNA) for the failing heart. The present study suggests that endogenous ET-1 is involved in the progression of heart failure, and that an ET receptor antagonist becomes a new drug for heart failure.
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