| Budget Amount *help |
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2004: ¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 2003: ¥7,300,000 (Direct Cost: ¥7,300,000)
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| Research Abstract |
In heart failure or hypertension, it has come to seem that not only circulating aldosterone but also tissue aldosterone has some pathophysiological meanings. In our laboratory, we continuously examined the study of cardiac Steroidogenesis and the relating hormones in humans. In our recently study, we found that aldosterone is secreted from the failing heart ; on the other hand, dehydroepiandrosterone(DHEA) is secreted from the control(healthy) heart in humans(Circulation 2004). In a sense, when the heart is healthy, it has the feature as zona reticularis of the adrenal gland ; however, when the heart condition is deteriorated, it appears the feature of zona glomerulosa. It is interesting to see the switching of the cascades to produce aldosterone or DHEA in relation to the heart conditions ; this is our big challenge of overlapping the concepts of the heart and the adrenal gland.
Furthermore, we recently clarified the ACTH secretion from the hearts(ventricles) of patients with hypertens
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ion(J Hypertens 2005). The amount of ACTH secreted from the ventricle was significantly correlated with the grade of blood pressure, suggesting a certain participation of cardiac ACTH to the pathophysiology of essential hypertension. Moreover, there was a positive correlation between cardiac ACTH secretion and cardiac aldosterone secretion, suggesting that, unlike the adrenal gland, ACTH may continue promoting synthesis of aldosterone in the heart. Thus, a new concept called cardiac Hypothalamus-Pituitary-Adrenal(HPA) system study was established in addition to the cardiac RAA system study.
Previously, we reported that aldosterone induces the gene expression of angiotensin-converting enzyme(ACE). On the other hand, we found a new action of aldosterone as for the inhibition of the ACE2 gene expression, which was via the mineralocorticoid receptor(MR). Augmentation of the ACE gene expression and inhibition of the ACE2 gene expression by aldosterone would contribute to the deformation of Angiotensin_<1-7> and formation of Angiotensin II, leading to worsening heart failure. Less
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