| Project/Area Number |
09670689
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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 | HOKKAIDO UNIVERSITY |
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Principal Investigator |
TOMITA Fumishi Hokkaido Univ., School of Med., Inst., 医学部, 助手 (40271655)
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| Co-Investigator(Kenkyū-buntansha) |
HATTORI Yuichi Hokkaido Univ., School of Med., Asso. Pro., 医学部, 助教授 (50156361)
KOHYA Tetsuro Hokkaido Univ. Medical Hospital, Lec., 医学部・附属病院, 講師 (70205350)
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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 |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | congestive heart failure / myocardial infarction / intracellular CaィイD12+ィエD1 handling / CaィイD12+ィエD1 sensitivity / ACE inhibitor / 細胞内Ca^<2+>ハンドリング |
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| Research Abstract |
We used the left coronary artery-ligated rat model of congestive heart failure. Left ventricular myocardial infarction (MI) was produced by ligation of the left coronary artery in Wistar-Kyoto rats at 10-12 weeks of age. Age-matched control rats underwent operation without coronary artery ligation (sham-operated control rats). ACE inhibitor therapy was begun 1 week after operation and was continued until week 6 after operation, when animal killed. To study the cellular mechanisms of the effects of ACE inhibition on the modification of the transition to failure in rat MI, we measured simultaneous intracellular CaィイD12+ィエD1 transients and myocyte shortening in isolated left ventricular myocytes from ACE-inhibitor treated MI rats, untreated MI rats, and sham-operated control rats. Collagenase-dissociated myocytes were loaded with indo 1-AM. In myocytes from untreated MI rats, the time to peak tension and the time to peak light were longer than those in the control. However, peak tension development and peak light, normalized for cell capacitance, were not different in the control and untreated MI. ACE inhibitor treatment improved the time course of both intracellular CaィイD12+ィエD1 transients and myocyte shortening. Maximal CaィイD12+ィエD1-activated force and CaィイD12+ィエD1 sensitivity of contractile protein were not different among the three groups. The present results indicate that ACE inhibitor-treatment improves the time course of intracellular CaィイD12+ィエD1 transients and myocyte shortenig in MI rats. This may contribute to the favorable effects whereby ACE inhibition modifies the transition from compensatory hypertrophy to failure.
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