Aldosterone, but not angiotensin II, reduces angiotensin converting enzyme 2 gene expression levels in cultured neonatal rat cardiomyocytes.
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.


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.


CONCLUSIONS
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.
Yamamuro
Megumi
M
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Yoshimura
Michihiro
M
Nakayama
Masafumi
M
Abe
Koji
K
Sumida
Hitoshi
H
Sugiyama
Seigo
S
Saito
Yoshihiko
Y
Nakao
Kazuwa
K
Yasue
Hirofumi
H
Ogawa
Hisao
H
D000450:Aldosterone / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D015536:Down-Regulation; D000077545:Eplerenone; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors
D000451:Mineralocorticoid Receptor Antagonists; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D000804:Angiotensin II; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2