| Project/Area Number |
09670691
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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 |
YAMAGUCHI Iwao University of Tsukuba Institute of Clinical Medicine, 臨床医学系, 教授 (30111389)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAUCHI Takashi University of Tsukuba Institute of Clinical Medicine, 臨床医学系, 講師 (60222329)
石川 智久 筑波大学, 基礎医学系, 講師 (10201914)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | heart failure / cardiac hypertrophy / arrhythmia / mechanical contraction / excitation / feedback / ion channel / フィードバック / 自立神経 |
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| Research Abstract |
The mechanical stress has been reported to affect the process of electrical excitation in the heart. This phenomenon is called to be "contraction-excitation feedback". Although it has been considered that the stretch activated ion channel is involved in its mechanisms, the precise mechanism is unclear.
We measured QT-interval as an indicator of electrical excitation in various conditions such as pressure-overload to the left ventricic, volume-overload to the left ventricle, valsalva stimulation, dysopyramide application. Furthermore, we also studied myocardial endothelin-1 and contraction- excitation feedback.
Cardiac myocytes as well as vascular endothelium produce endothelin (ET)-1. In the heart, ET-1 induces myocardial hypertrophy and causes cellular injury of cardiac myocytes. In this study, we investigated roles of ET-1 in heart diseases such as chronic heart failure (CHF) and cardiac hypertrophy. We used coronary artery-ligated rat model as a CHF model animal (CHF rats). It was rev
… More
ealed that production of ET-1 (both peptide and mRNA levels) is increased in the ailing heart of the CHF rats. We also obtained the data that the upregulated myocardial ET-1 system may play an aggravating role in the progression of CHF, because long-term (12 weeks) treatment with the ET receptor antagonist BQ-123 greatly improved survival rate of CHF rats. Twelve weeks after BQ-123 application, survival rate of the GHF rats treated with BQ-123 (CHF-BQ rats) was markedly higher than that of the CHF rats treated with saline alone (CHF-saline rats) (85% vs 43%, P< 0.01).
Hemodynamic parameters of surviving rats were ameliorated by chronic BQ-123 treatment. BQ-123 treatment effectively prevented unfavorable ventricular remodeling of the CHF rats. In the hypertrophied left ventricle of the aorta-banded rats, the expression of ET-1 mRNA was significantly increased. Treatment with BQ-123 for 7 days significantly reduced cardiac hypertrophy of the aorta- banded rats. In these rats treated with BQ-123, the expression of mRNA of myocardial ion channels was altered.
These findings suggest that contraction-excitation feedback mechanism is involved in arrhythmias in heart failure and cardiac hypertrophy. Less
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