| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
We serially measured cardiac AM levels in pressure- and volume-over loaded heart failure in rats. Cardiac AM levels increased in a time dependent manner with a concomitant increase of left ventricular weight. Left ventricular AM levels were correlated with the gene expression of fetal cardiac molecular marker such as β-MHC and α-actin. In myocardial infarction rat model, peptide and gene expression of AM levels were increased in infarct regions in acute phase of myocardial infarction. In cultured cardiac rat fibroblast, AM significantly inhibited proliferation and collagen production of cardiac fibroblast.
In rat heart failure model, renal tissue AM levels were also increased and immunohistochemical study revealed that AM was stained strongly in collecting duct, distal tubules, and glomerulus. With regard to the mechanism of increased renal AM, mRNA levels of AM were increased, however, mRNA levels of AM receptors did not change. Renal AM levels significantly correlated with urinary sod
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ium excretions.
We also studied the effect of acute administration of AM in heart failure rats. Acute AM administration significantly increased cardiac output, renal blood flow, glomerular filtration rate, urinary flow, and urinary sodium excretion and significantly decreased blood pressure, peripheral vascular resistance, and right ventricular systolic pressure. We also examined the effects of acute administration of AM in patients with heart failure. Acute administration of AM significantly improved homodynamics, neurohumoral factors, and renal function.
In addition, we measured two molecular forms of AM in plasma and urine using recently developed immunoradiometric assay in patients with cardiovascular diseases. Plasma contains higher percentage of inactive molecular form AM ( >80%) than active molecular form of AM.Whereas urine contains higher percentage of active AM than plasma. Both molecular forms of AM were increased in essential hypertension, chronic renal failure, and heart failure in proportion to its clinical severity.
These results suggest that AM may be deeply-involved in the pathophysiology in the cardiovascular disease and that AM may compensate the pathophysiology of cardiovascular disease as a defense mechanism. In addition, cardiac AM levels may be a biochemical marker for cardiac hypertrophy and cadiac remodeling. Intravenous infusion of AM may be a new therapeutic approach in the treatment of heart failure. Less
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