| Project/Area Number |
10670043
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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 |
General physiology
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| Research Institution | Shimane Medical University |
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Principal Investigator |
HASHIMOTO Michio Shimane Medical University, Department of Physiology, Instructor, 医学部, 助手 (70112133)
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| Co-Investigator(Kenkyū-buntansha) |
NOSAKA Seishi Shimane Medical University, Department of Surgery, Instructor, 医学部, 助手 (10294373)
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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 |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Endocardial endothelial cells / Mechanoreceptor / Shear stress / Transmural pressure / Prostacycline / Aging / Heart failure / Rats / 心不全 / 一酸化窒素 / 細胞内Caストアー |
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| Research Abstract |
We estimated the effects of mechanical stress such as shear stress and transmural pressure on the production of vasoactive substances from endocardial endothelial cells (EECs) isolated from porcine hearts and from young (5-week-old) and aged (100-week-old) rat hearts. We also demonstrated age-related changes in rat cardiac functions, with the Langendorff and Working heart apparatus.
Results and Conclusion
1 : Shear stress (0.2〜6dyne/cmィイD12ィエD1) and transmural pressure (0〜150mmHg) increased prostacycline (PGIィイD22ィエD2) production from porcine EECs. Shear stress-induced PGIィイD22ィエD2 production was significantly inhibited from cells exposed to 8-(dimetylamino) octyl 3, 4, 5-trimethoxybenzoate hydrochloride (an inhibitor of intracellular calcium mobilization) or cyclopiazonic acid ( and endoplasmic reticulum CaィイD12+ィエD1-ATPase inhibitor) ; moreover, the production decreased from EECs of aged rats rather than from those of young rats.
2 : Proliferation of rat EECs decreased with aging, in association with the morphological enlargement of the cells.
3 : Phase-contrast electron microscopy revealed the enlargement of right ventricular EECs isolated from rat hearts with right ventricular hypertrophy induced by subcutaneous injection of monocrotaline.
4 : Cardiac output, aortic flow and heart rates of rats decreased significantly with advancing age.
Shear stress enhances PGIィイD22ィエD2 production from EECs, and the mechanotransduction of shear stress depends on calcium mobilization in EECs. in rats mechanotransduction decreased with aging, and, morphologically, the right ventricular EECs enlarged with advancing age and with right ventricular hypertrophy. These results suggest that endocardial dysfunction participates in the development of heart failure.
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