Pathosignificance of cardiac aldosterone synthesis in heart failure

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Extra-adrenal aldosterone synthase system has been closed-up recently and we also showed that aldosterone was synthesized and secreted from human failing or hypertensive heart. And we recently showed that cardiac aldosterone synthesis is suppressed by ACE inhibitor.Still more detailed examination was performed about the human cardiac aldosterone synthesis. The cardiac tissue was extracted from the autopsy of patients with heart failure or non-heart failure and we examined gene expression of CYP11B2, aldosterone synthase. Since the expression of CYP11B2 was very small, we could not detect them by usual real-time RT-PCR method. Then, we newly modified real-time RT-PCR and we were able to detect the gene expression and quantified them. Consequently, the gene expression of CYP11B2 was up-regulated in the failing heart compared with the non-failing heart.Next, the inhibitory effect of natriuretic peptide (NP) on cardiac aldosterone synthesis was examined using neonatal rat cardiocyte culture system. By blocking endogenous natriuretic peptide effect with HS142-1, a GC-A receptor antagonist, CYP11B2 gene was significantly expressed. Also, exogenous natriuretic peptide suppressed the CYP11B2 gene expression, the dose of which was a commonly used concentration level in the treatment of heart failure. These results indicate that cardiac aldosterone synthesis is suppressed by NP and the balancing between aldosterone and NP would be very important in heart failure status.As for pathophysiological roles of aldosterone, we recently found that aldosterone augments the ACE gene expression in neonatal rat cardiocytes, making a vicious cycle between tissue RAAS.As mentioned above, we have studied about cardiac aldosterone synthesis and its pathophysiological significance in heart failure. In he renin-angiotensin-aldosterone system, not only angiotensin II but also aldosterone would provide unfavorable effects directly. The aspect of a paradigm shift has just been presented.