| Project/Area Number |
05670100
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General pharmacology
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| Research Institution | Osaka City University |
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Principal Investigator |
IWAO Hiroshi Osaka City University, Medical School, Professor, 医学部, 教授 (00137192)
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1994: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1993: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Angiotensin / Receptor / Heart / Kidney / Blood pressure / Angiotensin II receptor antagonist / Organ damages / TGF-beta1 / ECM / Phenotype |
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| Research Abstract |
Accumulating evidence indicated that transforming-beta1 and extracellular matrix components may be responsible for cardiovascular injury. The increase in collagen matrices in the heart enhances organ stiffness and results in left ventricular diastolic dysfunction, which finally contributes to cardiac failure. Pathological left ventricular hypertrophy, by pressure overload, is accompanied not only by the quantitative change (myocyte hypertrophy) but also by the qualitative changes, including the shift to fetal phenotype of myocytes and interstitial fibrosis. Recent investigation, using cultured cells from the neonatal rat heart, show that angiotensin II in vitro directly causes hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts via AT1 receptor, and that angiotensin II in vitro induces fetal phenotype of genes in cardiac myocytes via AT1 receptor. In this study show that cardiac AT1 receptor in vivo play a critical role in left ventricular hypertrophy, myocardial phenotypic change and interstitial collagen expression of hypertension. The improvement of hypertension-induced left ventricular hypertrophy and molecular changes by AT1 receptor antagonist may be at least in part mediated by its direct action, independent of its hypertensive effect.
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