Aldosterone, but Not Angiotensin II, Reduces Angiotensin Converting Enzyme 2 Gene Expression Levels in Cultured Neonatal Rat Cardiomyocytes

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Background A previous report showed that aldosterone upregulates angiotensin converting enzyme (ACE) gene expression levels in cultured neonatal rat cardiocytes. ACE2 is a novel homologue of ACE, which exists in the human heart, and ACE2 converts angiotensin I to angiotensin 1-9 and angiotensin n to angiotensin 1-7, there-by decreasing angiotensin n levels. In the present study, an investigation took place to see whether aldosterone regulates the expression of ACE2 as well as that of ACE in cultured neonatal rat cardiomyocytes. Methods and Results Primary neonatal rat cardiomyocytes were cultured with aldosterone. Total RNA was extracted from these cardiomyocytes and quantified the mRNA levels of ACE2, ACE and GAPDH by using realtime reverse transcription polymerase chain reaction analysis. Aldosterone significantly decreased ACE2 mRNA levels and increased ACE mRNA levels at 12h. Angiotensin II, however, had no effect on either ACE2 mRNA levels or ACE mRNA levels. Eplerenone, a mineralocorticoid receptor antagonist, completely blocked the increase in ACE mRNA levels and the reduction in ACE2 mRNA levels due to aldosterone. Conclusion Aldosterone, but not angiotensin n, reduced ACE2 mRNA levels and increased ACE mRNA levels in rat cardiomyocytes via mineralocorticoid receptor. Aldosterone might play an important role in cardiac remodeling by upregulating ACE and downregulating ACE2 levels.
社団法人日本循環器学会の論文
2008-07-20