(Circulation. 2001;104:137.)
© 2001 American Heart Association, Inc.
Brief Rapid Communications |
Aldosterone Induces Angiotensin-Converting-Enzyme Gene Expression in Cultured Neonatal Rat Cardiocytes
From the Department of Cardiovascular Medicine, Kumamoto University School of Medicine (E.H., M.Y., M. Nakayama, Y.S., T.I., S.N., H.O.); the Division of Cardiology, Kumamoto Aging Research Institute (H.Y., Y.M.), Kumamoto; and the Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine (O.N., M. Nakagawa, M.H., K.K., Y.S., K.N.), Kyoto, Japan.
Correspondence to Michihiro Yoshimura, MD, Department of Cardiovascular Medicine, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto, 860-8556, Japan. E-mail: bnp{at}kumamoto-u.ac.jp
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 (EC50, 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.
Key Words: angiotensin • aldosterone • polymerase chain reaction • cells
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|
|
|
|
|
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|
|
|
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|
|
|
|
|
|
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|
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|
|
|
|
 |
|
 B. Pitt A New HOPE for Aldosterone Blockade? Circulation, September 28, 2004; 110(13): 1714 - 1716. [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
 H. T. Yu Progression of Chronic Renal Failure Arch Intern Med, June 23, 2003; 163(12): 1417 - 1429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
R. B. Felder, J. Francis, Z.-H. Zhang, S.-G. Wei, R. M. Weiss, and A. K. Johnson Heart failure and the brain: new perspectives Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2003; 284(2): R259 - R276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Francis, R. M. Weiss, A. K. Johnson, and R. B. Felder Central mineralocorticoid receptor blockade decreases plasma TNF-alpha after coronary artery ligation in rats Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2003; 284(2): R328 - R335. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 M. Yoshimura, S. Nakamura, T. Ito, M. Nakayama, E. Harada, Y. Mizuno, T. Sakamoto, M. Yamamuro, Y. Saito, K. Nakao, et al. Expression of Aldosterone Synthase Gene in Failing Human Heart: Quantitative Analysis Using Modified Real-Time Polymerase Chain Reaction J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3936 - 3940. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Hayashi, M. Ohtani, T. Hiraishi, and Y. Kobayashi Postoperative synthetic human atrial natriuretic peptide infusion and oral spironolactone administration for a patient with giant atria and low plasma level of atrial natriuretic peptide J. Thorac. Cardiovasc. Surg., July 1, 2002; 124(1): 206 - 209. [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
A. Goette, U. Lendeckel, and H. U Klein Signal transduction systems and atrial fibrillation Cardiovasc Res, May 1, 2002; 54(2): 247 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D Struthers Review: Aldosterone-induced vasculopathy: a new reversible cause of cardiac death Journal of Renin-Angiotensin-Aldosterone System, December 1, 2001; 2(4): 211 - 214. [PDF]
|
|