| Project/Area Number |
09670776
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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 | NATIONAL CARDIOVASCULAR CENTER RESEARCH INSTITUTION |
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Principal Investigator |
NISHIKIMI Toshio National Cardiovascular Center Research Institute, Etiology and Pathogenesis, Senior Staff, 病因部, 室長 (80291946)
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| Co-Investigator(Kenkyū-buntansha) |
KANGAWA Kenji National Cardiovascular Center Research Institute, Biochemistry, Director, 生化学部, 部長 (00112417)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | adrenomedullin(AM) / hypertension / heart failure / pulmonary hypertension / cardiac myocytes / cardiac nonmyocytes / myocardial infarction / アドレノメデュリン |
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| Research Abstract |
We investigated the effect of heart failure on tissue AM and mRNA levels in rat. Tissue AM and mRNA levels in the heart and lung are significantly increased in heart failure group than in sham - operated group. We also examined the secretion of AM in human failing heart. Plasma AM levels of coronary sinus are significantly higher than those of aorta in patients with heart failure, suggesting that failing heart in human actually secrets AM into the circulation. In the cultured cardiac myocytes and nonmyocytes, both of these cells secret AM into the media and AM increases cAMP in both cells, In the regulation of production of AM, angiotensin II, endothelin and phenylephrine did not increase AM into the media in these cells. However, interleukin -1beta and tumor necrosis-alpha significantly increased AM secretion and AM gene expression in both cells. These results suggest that increased AM in the failing heart may be associated with cytokines and may increase cAMP levels in myocytes and n
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onmyocytes as an autocrine and paracrine factor and may modulate cardiac function and pathophysiology in the failing heart.
Plasma AM levels are significantly higher in essential hypertensive patients with left ventricular hypertrophy or with decreased distensibility of carotid artery than those without target organ damage. Plasma AM levels in acute myocardial infarction reached peak at 24- 48 hours after onset of the disease. Peaked AM levels correlated with myocardial infarct size. During cardiac surgery plasma AM levels significantly increased after reperfusion of the lungs and its peak levels correlated with operation time. These results suggest that plasma AM levels may reflect the target organ damage in essential hypertensive subjects, the myocardial infarct size in acutemyocardial infarction and the degree of operative invasion after cardiac surgery.
We also assessed the effect of chronic infusion of AM in pulmonary hypertensive rats. Chronic AM infusion significantly increased plasma AM levels by two fold compared with those of control rats. However, it significantly reduced the right ventricular systolic pressure, right ventricular weight and medial thickening of pulmonary artery. These results suggest that increased plasma AM levels in pulmonary hypertension may attenuate the development of pulmonary hypertension and that AM infusion may be a new therapeutic approach in pulmonary hypertension. Less
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