1997 Fiscal Year Final Research Report Summary
Adrenomedullin as a Therapentic or Ddiagnostic Tool in Cardiovascular Diseases
| Project/Area Number |
07557059
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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) |
TERAOKA Hiroshi Shionogi & Co.Ltd., Diag Sci Div, General Manager, 研究室, 部長研究員
KANGAWA Kenji National Cardiovascular Research Institute, Dept Biochem, Director, 生化学部, 部長 (00112417)
KITAMURA Kazuo Miyazaki Medical College, 1st Dept Intern Med, Associate Professor, 医学部, 講師 (50204912)
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| Project Period (FY) |
1995 – 1997
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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 is reported to be present 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. Both 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 AM is a useful parameter in diagnosis and evaluation of the patients. 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 asssays, we will be able to clarify the pathophysiological roles of the two molecular forms of AM in plasma.
Therapeutic approach :
Many of the biological actions of AM had been tested by using unphysiologically high doses of AM for a short period of time. To examine the effect of chronically administered AM,we infuesed synthetic AM at a relative low dose to conscious unrestrained 2-kidney, 1-clip renovascular hypertensive rats for two weeks. Chronically infused AM had a significant blood pressure-lowering effect accompanied by reduced plasma renin activity and aldosterone concentration at plasma AM level within a physiological range. Thus, we may be able to use AM,AM analogues or inhibitor of enzyme which cleaves AM as therapeutic agents for hypertension. In addition, we found that AM attenuates hypertrophy of cultured rat cardiac myocytes and that AM improve pulmonary congestion in rat model of congestive heart failure. These results suggest AM may be useful as a therapeutic tool in many of the cardiovascular diseases.
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Research Products
(14 results)
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[Publications] Kitamura, K., Kato, J., Kawamoto, M., Tanaka, M., Chino, N., Kangawa, K.and Eto, T.: "Intermediate form of glycine-extended adrenomedullin is major circlating molecular form in human plasma." Biochem.Biophys.Res.Commun.244. 551-555 (1998)
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[Publications] Ishiyama, Y., Kitamura, K., Kato, J., Sakata, J., Kangawa, K.and Eto, T.: "Changes in cardiac adrenomedullim concentration in renovascular hypertensive rats." Hypertens.Res.20. 113-117 (1997)
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[Publications] Kuwasako, K., Kitamura, K., Ishiyama, Y., Washimine, H., Kato, J., Kangawa, K.and Eto, T.: "Purification and characterization of PAMP-12 (PAMP[9-20]) in porcine adrenal medulla as a major endogenous biologically active peptide." FEBS Lett.414. 105-110 (1997)
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[Publications] Tsuruda, T., Kato, J., Kitamura, K., Kuwasako, K., Imamura, T., Koiwaya, Y., Tsuji, T., Kangawa, K.and Eto, T.: "Adrenomedullin : A possible autocrine or paracrine inhibitor of hypertrophy of cardiomyocytes." Hypertension. 31. 505-510 (1998)
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「研究成果報告書概要(欧文)」より
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