Relationship between β-adrenergic signaling pathway and cytokines in hypertensive heart failure.
| Project/Area Number |
10670689
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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 | Kurume University |
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Principal Investigator |
IWAMI Gensho Kurume University, school of Medicine,Department of Medicine III, Assistant Professor, 医学部, 講師 (90203405)
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| Co-Investigator(Kenkyū-buntansha) |
KIKUCHI Toshio Kurume University, school of Medicine,Department of Medicine III, Instructor, 医学部, 助手 (20289432)
OKA Naoki Kurume University, school of Medicine,Department of Medicine III, Instructor, 医学部, 助手 (00299421)
西 宏文 久留米大学, 医学部, 講師 (60189248)
中田 真詩 久留米大学, 医学部, 講師 (70180304)
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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: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | heart failure / β-adrenergic pathway / Adenylyl cyclase / cytokine / β-受容体 / アデニル酸シクラーゼ / β-受容体リン酸化酵素 / BNP / IGF-1 |
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| Research Abstract |
[Purpose] The cardiac β-adrenergic pathway is downregulated in heart failure. There are conflicting reports about the change of down stream of β-adrenergic signaling pathways in heart failure. We examined βAR, adenylyl cyclase (AC), βAR kinase 1 (βARK 1) and G protein coupled receptor kinase (GRK5) in heart failure (HF) of Dahl salt-sensitive rats (DS). Also we examined how cytokines inhibited the cardiac β-adrenergic pathway.
[Result] Echocardiography showed that DS- fed an 8 % NaCl diet developed left ventricular (LV) hypertrophy at 18 wk, followed by marked LV systolic dysfunction. The HF rats had increased plasma norepinephrine associated with decrease of βAR. The amount of βARK 1 and GRK5 in cytosolic fraction were increased in the HF rats. AC activity of LV membrane fraction was decreased, and also northern blotting showed that AC type V mRNA was decreased in the HF rats. In the HF rats, cardiac lL-1β and TNFa were increased. Also in vitro lL-1 β and TNFα inhibited cardiac AC activities which stimulated by isoproterenol and GTPgS. However, AC activity stimulated by forskolin did not show any inhibition of lL-1β and TNFa.
[Conclusion] The data suggests that high salt diet causes hypertensive heart failure in DS by a mechanism which may involve down regulation of the pathway from down stream to β-adrenoceptor. And lL-1 β and TNFα may involve interaction between β-adrenoceptor and G-protein.
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Report
(3 results)
Research Products
(6 results)
