| Project/Area Number |
10670678
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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 | Nippon Medical School |
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Principal Investigator |
KIUCHI Kaname Nippon Medical School, First Department Assistant of Internal Medicine, 医学部, 助手 (50260972)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAGI Gen Nippon Medical School, First Department of Internal Medicine, Assistant, 医学部, 助手
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | hart failure / β-receptro / catecholamine / Gs / Adenylyl cyclare / high-affinity β-receptor / 心不全 |
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| Research Abstract |
The development of pacing-induced heart failure was studied in chronically instrumented, conscious dogs paced at a rate of 240 bpm for 1 day (n=4), 1 week (n=3), and 4-7 weeks (n=4). Left ventricular (LV) dP/dt was decreased at 1 day, LV end-diastolic pressure and heart rate were increased at 1 week, but clinical signs of heart failure were only observed after 4-7 weeks of pacing. The LV dP/dt responses to isoproterenol were depressed even after 1 day pacing. Both the fraction of β -adrenergic receptors binding agonist with high affinity, adenylyl cyclase activity, and ryanodine receptor density decreased after 1 day of pacing. ΒィイD21ィエD2-adrenergic receptor density was decreased after 1 week. The functional activity of Gs was not reduced, the GィイD2iα2ィエD2 rose after 4-7 weeks of pacing. The fraction of β -adreberguc receotirs bubdubg aginist with high affinity correlates LV dP/dt responses to catechoamine. Thus, the mechanism of β -adrenergic receptor dysfunction in pacing-induced heart failure is characteized initially by uncoupling of β -adrenergic receptors, and a defect in the adenylyl cyclase catalytic unit. Selective down-regulation of βィイD21ィエD2 -adrenergic receptors and increases in Gi occur as later events.
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