title: Aldosterone induces angiotensin-converting-enzyme gene expression in cultured neonatal rat cardiocytes.
abstract: BACKGROUND
  The cardiac renin-angiotensin-aldosterone system is activated in failing hearts in proportion to the severity of the disease. We hypothesized that a positive feedback mechanism might exist within this system and contribute to the progression of the heart failure. Methods and Results-- To test this hypothesis, we examined whether angiotensin II or aldosterone induces the expression of angiotensin-converting-enzyme (ACE) mRNA in cultured neonatal rat ventricular cardiocytes. Expression of ACE mRNA was detected and quantified using real-time reverse transcription-polymerase chain reaction. Exposure to angiotensin II (10(-5) mol/L) for 24 hours had no significant effect on the expression of ACE mRNA (0.7+/-0.5-fold versus control, P=NS), but similar treatment with aldosterone (10(-5) mol/L) induced a 23.3+/-7.9-fold increase (P<0.01) in ACE mRNA expression. The effect of aldosterone was both time- (maximal effect, 24 hours) and dose-dependent (EC(50), 4x10(-7) mol/L), and it was significantly (P<0.01) inhibited by spironolactone, a specific mineralocorticoid receptor antagonist.
  
  
  CONCLUSIONS
  Aldosterone upregulates ACE mRNA expression, which is blocked by spironolactone in neonatal rat cardiocytes. Thus, spironolactone may suppress the progression of heart failure by blocking the effects of aldosterone and angiotensin II.
authors.affiliation: Department of Cardiovascular Medicine, Kumamoto University School of Medicine, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Harada
authors.forename: M
authors.initials: M
authors.lastname: Yoshimura
authors.forename: H
authors.initials: H
authors.lastname: Yasue
authors.forename: O
authors.initials: O
authors.lastname: Nakagawa
authors.forename: M
authors.initials: M
authors.lastname: Nakagawa
authors.forename: M
authors.initials: M
authors.lastname: Harada
authors.forename: Y
authors.initials: Y
authors.lastname: Mizuno
authors.forename: M
authors.initials: M
authors.lastname: Nakayama
authors.forename: Y
authors.initials: Y
authors.lastname: Shimasaki
authors.forename: T
authors.initials: T
authors.lastname: Ito
authors.forename: S
authors.initials: S
authors.lastname: Nakamura
authors.forename: K
authors.initials: K
authors.lastname: Kuwahara
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.forename: K
authors.initials: K
authors.lastname: Nakao
authors.forename: H
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D000450:Aldosterone / Q000494:pharmacology*; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002138:Calibration; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008168:Lung / Q000737:chemistry / Q000378:metabolism; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013148:Spironolactone / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D012333:RNA, Messenger; D000804:Angiotensin II; D013148:Spironolactone; D000450:Aldosterone; D007703:Peptidyl-Dipeptidase A