| Project/Area Number |
12670646
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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 Iwa University of Tsukuba, Institute of Clinical Medicine, Professor, 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, Assistant Professor, 臨床医学系, 講師 (60222329)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | arrhythemia / heart failure / ion channel / electrical excitation / mechanical contraction / feed back / interaction / human and animals / 不全心筋 / 自律神経システム / 機械的收縮機構 |
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| Research Abstract |
The "contraction-excitation feedback" mechamsm. exists in the heart. 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 ventricle, valsalva stimulation, dysopyramide application. Furthermore, we also studied myocardial endothelin-1 and contraction-excitation feedback.
Cardiac myocytes as well as vascular endothelium produce othelin (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 modelas a CHF model ani
… More
mal (CHF rats). It was revealed that production of ET-1 (both peptide and mRNA levels) is increased in the failing heart of the CHE 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 CHE rats. Twelve weeks after BQ-123 application, survival rate of the CHF rats treated with BQ-123 (CHF-BQ rats) was markedly higher than that of the CHF rats tre4ted with saline alone (CHF-saline rats). 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 data suggest that contraction-excitation feedback mechanism is involved in arrhythmias in heart failure in experimental animals and in humans. Less
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