| Project/Area Number |
11557057
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Miyazaki Medical College |
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Principal Investigator |
ETO Tanenao Miyazaki Medical College, 1st Dept Intern Med, Professor, 医学部, 教授 (10038854)
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| Co-Investigator(Kenkyū-buntansha) |
KITA Toishihiro Miyazaki Medical College, 1st Dept Intern Med, Research Associate, 医学部, 助手 (70315365)
KATO Johji Miyazaki Medical College, 1st Dept Intern Med, Research Associate, 医学部, 助手 (20274780)
KITAMURA Kazuo Miyazaki Medical College, 1st Dept Intern Med, Associate Professor, 医学部, 講師 (50204912)
SAKATA Tsuneaki Shionogi & Co. Ltd., Diag Sci Div, Chief Investigator, 医科学研究所, 主任研究員
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| Project Period (FY) |
1999 – 2001
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| Keywords | Adrenomedullin / PAMP / cAMP / Assay methods / Amidation / Hypotensive peptide / Receptor / Cleavage enzyme |
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| Research Abstract |
Diagnostic approach :
Adrenomedullin circulates in the human blood. We have shown that immunoreactive AM in the human plasma consists of two molecular forms of peptides : a mature AM with an amidated C-terminus and an intermediate form of glycine-extended AM, and the intermediate AM may be converted to the mature form in the human blood. To measure the plasma AM without extraction procedure, we have developed immunoreactive radiometric assays (IRMAs) for AM. Two types of IRMAs have been established : one can detect only the mature AM and the other reacts both the mature and intermediate AM. By using these assays, we clarified that the mature and intermediate AM levels in plasma are found to be elevated in patients with hypertension, heart failure or renal failure at almost a constant ratio, the elevation of plasma AM was closely related to severity of the diseases, suggesting that two forms of AM are useful parameters in diagnosis and evaluation of the patients.
Therapeutic approach :
We have prepared recombinant human AM (rhAM). Using this peptide we examine the effects of continuous administration of AM on hemodynamics, heart weight, plasma hormone levels and LV collagen volume fraction (CVF) in myocardial infarction (MI) rats. Intravenous infusion of rhAM was started immediately after the surgery by osmotic mini-pump and continued for 4 weeks. When compared with control, the AM infusion significantly decreased LV end-diastolic pressure and heart weight/body weight with reduced plasma endogenous rat AM and ANP levels, while it had no effects on infarct size and arterial blood pressure. CVF in non-infarct LV area measured by Sirius red staining was also significantly reduced in MI-AM compared with MI-S. Thus, continuous administration of AM ameliorated LV dysfunction and inhibited LV remodeling in Ml rats. These findings suggest not only a role of AM in modulating LV remodeling but also a possibility for AM as the therapeutic tool for acute MI.
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