Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Experimental Investigation
Aldosterone, but Not Angiotensin II, Reduces Angiotensin Converting Enzyme 2 Gene Expression Levels in Cultured Neonatal Rat Cardiomyocytes
Megumi YamamuroMichihiro YoshimuraMasafumi NakayamaKoji AbeHitoshi SumidaSeigo SugiyamaYoshihiko SaitoKazuwa NakaoHirofumi YasueHisao Ogawa
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JOURNAL FREE ACCESS

2008 Volume 72 Issue 8 Pages 1346-1350

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Abstract

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 II to angiotensin 1-7, thereby decreasing angiotensin II 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 real-time reverse transcription polymerase chain reaction analysis. Aldosterone significantly decreased ACE2 mRNA levels and increased ACE mRNA levels at 12 h. 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 II, 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. (Circ J 2008; 72: 1346 - 1350)

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© 2008 THE JAPANESE CIRCULATION SOCIETY
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