| Project/Area Number |
11838020
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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 Institution | Research Institute for Production Development |
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Principal Investigator |
KISHIMOTO Ichiro Research Institute for Production Development, Research Fellow, 成人病科学研究室, 研究員 (80312221)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Yoshihiko Kyoto University, Department of Medicine and Clinical Science, Associate Professor, 医学研究科, 助教授 (30250260)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Guanylyl Cyclase-A / Atrial Natriuretic Peptide / Brain Natriuretic Peptide / Cardiac Hypertrophy / Angiotensin Recepter / Cardiac Fibrosis / 心臓リモデリング / アンギオテンシン / ナトリウム利尿ペプチド受容体 / グアニリルシクラーゼ / 遺伝子操作マウス / 心筋梗塞 / 虚血・再灌流 / レニン・アンギオテンシン系 |
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| Research Abstract |
The mice deficient for guanylyl cyclase (GC)-A, a receptor for natriuretic peptides, display marked cardiac hypertrophy and interstitial fibrosis. In the present study, we examined the mechanism of the hypertrophy and exaggerated fibrosis in GC-A knock out (KO) mice. Since the renin-angiotensin system plays an important role for the establishment of cardiac hypertrophy and fibrosis, we studied the effect of angiotensin II type I receptor (AT1R) antagonist on the heart of GC-A KO.Treatment of GC-A KO with AT1R antagonist dramatically reduced cardiac hypertrophy and fibrosis. Treatment with hydralazine or 6-OHDA decreased blood pressure but these agents did not reduce cardiac hypertrophy. There were marked increases in TGF-b, collagen I and collagen III mRNA expression in the heart of GC-A KO and the augmented gene expressions were also decreased in AT1R antagonist-treated mice To confirm the above results, we next established the mice deficient for both GC-A and AT1R which showed similar reductions in cardiac hypertrophy and fibrosis. Taken together, these results suggested that the natriuretic peptide-GC-A pathway has inhibitory actions on the exaggerated angiotensin system. Therefore, the endogenous natriuretic peptide-GC-A pathway acts in a cardioprotective manner.
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