| Project/Area Number |
08838001
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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 |
老化(加齢)
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| Research Institution | Yamagata University |
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Principal Investigator |
KATANO Yumi YAMAGATA UNIVERSITY SCHOOL OF MEDICINE,PROFESSOR., 医学部, 教授 (70018696)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIHATA Akira YAMAGATA UNIVERSITY SCHOOL OF MEDICINE,INSTRUCTOR., 医学部, 助手 (40232326)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1996: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Endothelin-1 / Endothelin-receptor / Endothelin-receptor mRNT / rat / aging / myocardium / positive inotropic effect / SR-Ca ATPase / 筋小胞体Ca^<2+>取り込み / 老化心筋細胞 / 老化平滑筋細胞 / 血管平滑筋収縮作用 / 遺伝子発現 |
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| Research Abstract |
Endothelin (ET) is an endogenous potent vasoconstrictor, which may be involved in the pathogenesis of various cardiovascular diseases. It has been known that a high density of ET receptors is found in mammalian myodardium and myocardial ET receptors are up-regulated in some pathologic states. We have found that ET-1-induced coronary vasoconstriction increased with age and myocardial ET receptors are up-regulated in aged rat in compare with young rat.
In this study we examined the mechanisms of the age-related changes in the cardiac response to ET-1 and gene expression of ET^A-and ET^B-receptors as well as age-related changes in the binding characteristics of ET receptor in rat ventricular myocardium.
Results : In experiments with isolated papillary muscles, ET-1 elicited a positive inotropic effect in the young rat, but not in aged rat. A SR-Ca-ATP ase inhibitor, cyclopiazonic acid, concentration-dependently inhibited the positive inotropic effects in the young rat. Receptor assay showed that the affinity of ET-receptor was not age-related differences, but the density (Bmax) of ET-binding was significantly increased in aged rats. Gene expression of both ET^A-and ET^B-receptors determined by Northern blotting analysis or semiquantitative RT-PCR increased in aged rats, but not significantly. The ratio of ET^A-and ET^B-receptors mRNA was not changed, suggesting that the alteration of responsiveness to ET is not due to the change in the ratio of ET^A-and ET^B-receptors. These findings suggest that the decrease in the function of SR Ca-ATP ase may be responsible for the marked attenuation of the ET-induced positive inotropic effects in the aged rat. Alternatively the increase in ET-receptor in aged rats may be an adaptation to decreased cardiac responsiveness to ET-1.
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