(Circulation. 2001;103:72.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Aldosterone Production Is Activated in Failing Ventricle in Humans
From the Division of Cardiology (Y.M., H.Y.), Kumamoto Aging Research Institute; Department of Cardiovascular Medicine (M.Y., T.S., H.O., K.K., E.H., M.N., S.N., T.I., Y. Shimasaki), Kumamoto University School of Medicine, Kumamoto; and Department of Medicine and Clinical Science (Y. Saito, K.N.), Kyoto University Graduate School of Medicine, Kyoto, Japan.
Correspondence to Hirofumi Yasue, MD, PhD, Division of Cardiology, Kumamoto Aging Research Institute, 6-8-1 Yamamuro, Kumamoto City 860-8518, Japan. E-mail yasue{at}juryo.or.jp
Background—Recent reports have indicated that aldosterone is produced in extra-adrenal tissues in animals. The present study was designed to examine whether aldosterone is produced in human heart.
Methods and Results—Plasma levels of aldosterone, BNP, and angiotensin-converting enzyme were measured in anterior interventricular vein (AIV), coronary sinus (CS), and aortic root (Ao), respectively, in 20 patients with left ventricular systolic dysfunction (LVSD), 25 patients with LV diastolic dysfunction (LVDD), and 23 control subjects. Aldosterone levels were significantly higher in AIV and CS than Ao in LVSD (98±10 versus 72±9 pg/mL, P<0.001, and 97±11 versus 72±9 pg/mL, P<0.001, respectively) and LVDD (87±10 versus 71±9 pg/mL, P<0.01, and 84±10 versus 71±9 pg/mL, P<0.01, respectively) groups, but no differences were observed in levels for these sites in the control group. Levels of ACE activity and BNP also were higher in AIV than Ao in both LV dysfunction groups. The difference in aldosterone levels between AIV and Ao and those in BNP and angiotensin-converting enzyme had a significant positive correlation with LVEDP and a significant negative correlation with LV ejection fraction in the LVSD group.
Conclusions—Production of aldosterone, angiotensin-converting enzyme, and BNP are activated in failing human ventricle in proportion to severity.
Key Words: aldosterone • angiotensin-converting enzyme • angiotensin • B-type natriuretic peptide • ventricles
This article has been cited by other articles:
 |
|
 |
|
  H. Otani, F. Otsuka, K. Inagaki, J. Suzuki, T. Miyoshi, Y. Kano, J. Goto, T. Ogura, and H. Makino Aldosterone Breakthrough Caused by Chronic Blockage of Angiotensin II Type 1 Receptors in Human Adrenocortical Cells: Possible Involvement of Bone Morphogenetic Protein-6 Actions Endocrinology, June 1, 2008; 149(6): 2816 - 2825. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. C. Connell, S. M. MacKenzie, E. M. Freel, R. Fraser, and E. Davies A Lifetime of Aldosterone Excess: Long-Term Consequences of Altered Regulation of Aldosterone Production for Cardiovascular Function Endocr. Rev., April 1, 2008; 29(2): 133 - 154. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kasama, T. Toyama, H. Sumino, N. Matsumoto, Y. Sato, H. Kumakura, Y. Takayama, S. Ichikawa, T. Suzuki, and M. Kurabayashi Additive Effects of Spironolactone and Candesartan on Cardiac Sympathetic Nerve Activity and Left Ventricular Remodeling in Patients with Congestive Heart Failure J. Nucl. Med., December 1, 2007; 48(12): 1993 - 2000. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-L. Ambroisine, J. Favre, P. Oliviero, C. Rodriguez, J. Gao, C. Thuillez, J.-L. Samuel, V. Richard, and C. Delcayre Aldosterone-Induced Coronary Dysfunction in Transgenic Mice Involves the Calcium-Activated Potassium (BKCa) Channels of Vascular Smooth Muscle Cells Circulation, November 20, 2007; 116(21): 2435 - 2443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Muto, N. Ueda, T. Opthof, T. Ohkusa, K. Nagata, S. Suzuki, Y. Tsuji, M. Horiba, J.-K. Lee, H. Honjo, et al. Aldosterone modulates If current through gene expression in cultured neonatal rat ventricular myocytes Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2710 - H2718. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. S. Hwang, G. Cirrincione, D. P. Thomas, R. J. McCormick, and M. O. Boluyt Aldosterone Antagonism Fails to Attenuate Age-Associated Left Ventricular Fibrosis J. Gerontol. A Biol. Sci. Med. Sci., April 1, 2007; 62(4): 382 - 388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Kasama, T Toyama, T Hatori, H Sumino, H Kumakura, Y Takayama, S Ichikawa, T Suzuki, and M Kurabayashi Effects of torasemide on cardiac sympathetic nerve activity and left ventricular remodelling in patients with congestive heart failure Heart, October 1, 2006; 92(10): 1434 - 1440. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Yamamuro, M. Yoshimura, M. Nakayama, K. Abe, M. Shono, S. Suzuki, T. Sakamoto, Y. Saito, K. Nakao, H. Yasue, et al. Direct Effects of Aldosterone on Cardiomyocytes in the Presence of Normal and Elevated Extracellular Sodium Endocrinology, March 1, 2006; 147(3): 1314 - 1321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Goette, K. Jentsch-Ullrich, M. Hammwohner, S. Trautmann, A. Franke, H. U. Klein, and A. Auricchio Cardiac uptake of progenitor cells in patients with moderate-to-severe left ventricular failure scheduled for cardiac resynchronization therapy. Europace, March 1, 2006; 8(3): 157 - 160. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Deschamps and F. G. Spinale Pathways of matrix metalloproteinase induction in heart failure: Bioactive molecules and transcriptional regulation Cardiovasc Res, February 15, 2006; 69(3): 666 - 676. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Ye, C. J. Kenyon, S. M. MacKenzie, A. S. Jong, C. Miller, G. A. Gray, A. Wallace, A. S. Ryding, J. J. Mullins, M. W. McBride, et al. The Aldosterone Synthase (CYP11B2) and 11{beta}-Hydroxylase (CYP11B1) Genes Are Not Expressed in the Rat Heart Endocrinology, December 1, 2005; 146(12): 5287 - 5293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Nattel Aldosterone antagonism and atrial fibrillation: time for clinical assessment? Eur. Heart J., October 2, 2005; 26(20): 2079 - 2080. [Full Text] [PDF]
|
|
|
|
|
|
T. Karram, A. Abbasi, S. Keidar, E. Golomb, I. Hochberg, J. Winaver, A. Hoffman, and Z. Abassi Effects of spironolactone and eprosartan on cardiac remodeling and angiotensin-converting enzyme isoforms in rats with experimental heart failure Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1351 - H1358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M C Connell and E. Davies The new biology of aldosterone J. Endocrinol., July 1, 2005; 186(1): 1 - 20. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Fraccarollo, P. Galuppo, I. Schmidt, G. Ertl, and J. Bauersachs Additive amelioration of left ventricular remodeling and molecular alterations by combined aldosterone and angiotensin receptor blockade after myocardial infarction Cardiovasc Res, July 1, 2005; 67(1): 97 - 105. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Fiebeler, J. Nussberger, E. Shagdarsuren, S. Rong, G. Hilfenhaus, N. Al-Saadi, R. Dechend, M. Wellner, S. Meiners, C. Maser-Gluth, et al. Aldosterone Synthase Inhibitor Ameliorates Angiotensin II-Induced Organ Damage Circulation, June 14, 2005; 111(23): 3087 - 3094. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Katada, T. Meguro, H. Saito, A. Ohashi, T. Anzai, S. Ogawa, and T. Yoshikawa Persistent Cardiac Aldosterone Synthesis in Angiotensin II Type 1A Receptor-Knockout Mice After Myocardial Infarction Circulation, May 3, 2005; 111(17): 2157 - 2164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kasama, T. Toyama, H. Kumakura, Y. Takayama, S. Ichikawa, T. Suzuki, and M. Kurabayashi Effects of candesartan on cardiac sympathetic nerve activity in patients with congestive heart failure and preserved left ventricular ejection fraction J. Am. Coll. Cardiol., March 1, 2005; 45(5): 661 - 667. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Kuster, E. Kotlyar, M. K. Rude, D. A. Siwik, R. Liao, W. S. Colucci, and F. Sam Mineralocorticoid Receptor Inhibition Ameliorates the Transition to Myocardial Failure and Decreases Oxidative Stress and Inflammation in Mice With Chronic Pressure Overload Circulation, February 1, 2005; 111(4): 420 - 427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Lal, J. P. Veinot, and F. H.H. Leenen Critical role of CNS effects of aldosterone in cardiac remodeling post-myocardial infarction in rats Cardiovasc Res, December 1, 2004; 64(3): 437 - 447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Funder Cardiac Synthesis of Aldosterone: Going, Going, Gone... ? Endocrinology, November 1, 2004; 145(11): 4793 - 4795. [Full Text] [PDF]
|
|
|
|
|
|
E. P. Gomez-Sanchez, N. Ahmad, D. G. Romero, and C. E. Gomez-Sanchez Origin of Aldosterone in the Rat Heart Endocrinology, November 1, 2004; 145(11): 4796 - 4802. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Nakamura, M. Yoshimura, M. Nakayama, T. Ito, Y. Mizuno, E. Harada, T. Sakamoto, Y. Saito, K. Nakao, H. Yasue, et al. Possible Association of Heart Failure Status With Synthetic Balance Between Aldosterone and Dehydroepiandrosterone in Human Heart Circulation, September 28, 2004; 110(13): 1787 - 1793. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Garnier, J. K. Bendall, S. Fuchs, B. Escoubet, F. Rochais, J. Hoerter, J. Nehme, M.-L. Ambroisine, N. De Angelis, G. Morineau, et al. Cardiac Specific Increase in Aldosterone Production Induces Coronary Dysfunction in Aldosterone Synthase-Transgenic Mice Circulation, September 28, 2004; 110(13): 1819 - 1825. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mano, T. Tatsumi, J. Shiraishi, N. Keira, T. Nomura, M. Takeda, S. Nishikawa, S. Yamanaka, S. Matoba, M. Kobara, et al. Aldosterone Directly Induces Myocyte Apoptosis Through Calcineurin-Dependent Pathways Circulation, July 20, 2004; 110(3): 317 - 323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kasama, T. Toyama, H. Kumakura, Y. Takayama, T. Ishikawa, S. Ichikawa, T. Suzuki, and M. Kurabayashi Effects of Intravenous Atrial Natriuretic Peptide on Cardiac Sympathetic Nerve Activity in Patients with Decompensated Congestive Heart Failure J. Nucl. Med., July 1, 2004; 45(7): 1108 - 1113. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. C. Luft Cardiac Angiotensin Is Upregulated in the Hearts of Unstable Angina Patients Circ. Res., June 25, 2004; 94(12): 1530 - 1532. [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Vasan, J. C. Evans, E. J. Benjamin, D. Levy, M. G. Larson, J. Sundstrom, J. M. Murabito, F. Sam, W. S. Colucci, and P. W. F. Wilson Relations of Serum Aldosterone to Cardiac Structure: Gender-Related Differences in the Framingham Heart Study Hypertension, May 1, 2004; 43(5): 957 - 962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Fletcher, A. N. Buch, H. C. Routledge, S. Chowdhary, J. H. Coote, and J. N. Townend Acute aldosterone antagonism improves cardiac vagal control in humans J. Am. Coll. Cardiol., April 7, 2004; 43(7): 1270 - 1275. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Tsybouleva, L. Zhang, S. Chen, R. Patel, S. Lutucuta, S. Nemoto, G. DeFreitas, M. Entman, B. A. Carabello, R. Roberts, et al. Aldosterone, Through Novel Signaling Proteins, Is a Fundamental Molecular Bridge Between the Genetic Defect and the Cardiac Phenotype of Hypertrophic Cardiomyopathy Circulation, March 16, 2004; 109(10): 1284 - 1291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D Struthers and T. M MacDonald Review of aldosterone- and angiotensin II-induced target organ damage and prevention Cardiovasc Res, March 1, 2004; 61(4): 663 - 670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Fraccarollo, P. Galuppo, S. Hildemann, M. Christ, G. Ertl, and J. Bauersachs Additive improvement of left ventricular remodeling and neurohormonal activation by aldosterone receptor blockade with eplerenone and ACE inhibition in rats with myocardial infarction J. Am. Coll. Cardiol., November 5, 2003; 42(9): 1666 - 1673. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. Cohn, I. S. Anand, R. Latini, S. Masson, Y.-T. Chiang, and R. Glazer Sustained Reduction of Aldosterone in Response to the Angiotensin Receptor Blocker Valsartan in Patients With Chronic Heart Failure: Results From the Valsartan Heart Failure Trial Circulation, September 16, 2003; 108(11): 1306 - 1309. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. H. Hostetter and H. N. Ibrahim Aldosterone in Chronic Kidney and Cardiac Disease J. Am. Soc. Nephrol., September 1, 2003; 14(9): 2395 - 2401. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Qin, A. E. Rudolph, B. R. Bond, R. Rocha, E. A.G. Blomme, J. J. Goellner, J. W. Funder, and E. G. McMahon Transgenic Model of Aldosterone-Driven Cardiac Hypertrophy and Heart Failure Circ. Res., July 11, 2003; 93(1): 69 - 76. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. C. White Aldosterone: Direct Effects on and Production by the Heart J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2376 - 2383. [Full Text] [PDF]
|
|
|
|
|
|
S. Kasama, T. Toyama, H. Kumakura, Y. Takayama, S. Ichikawa, T. Suzuki, and M. Kurabayashi Addition of Valsartan to an Angiotensin-Converting Enzyme Inhibitor Improves Cardiac Sympathetic Nerve Activity and Left Ventricular Function in Patients with Congestive Heart Failure J. Nucl. Med., June 1, 2003; 44(6): 884 - 890. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Brown Eplerenone: Cardiovascular Protection Circulation, May 20, 2003; 107(19): 2512 - 2518. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Casal, J.-S. Silvestre, C. Delcayre, and A. M. Capponi Expression and Modulation of Steroidogenic Acute Regulatory Protein Messenger Ribonucleic Acid in Rat Cardiocytes and after Myocardial Infarction Endocrinology, May 1, 2003; 144(5): 1861 - 1868. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kasama, T. Toyama, H. Kumakura, Y. Takayama, S. Ichikawa, T. Suzuki, and M. Kurabayashi Effect of spironolactone on cardiacsympathetic nerve activity and left ventricular remodeling in patients with dilated cardiomyopathy J. Am. Coll. Cardiol., February 19, 2003; 41(4): 574 - 581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ito, M. Yoshimura, S. Nakamura, M. Nakayama, Y. Shimasaki, E. Harada, Y. Mizuno, M. Yamamuro, M. Harada, Y. Saito, et al. Inhibitory Effect of Natriuretic Peptides on Aldosterone Synthase Gene Expression in Cultured Neonatal Rat Cardiocytes Circulation, February 18, 2003; 107(6): 807 - 810. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. I. McFarlane and J. R. Sowers Aldosterone Function in Diabetes Mellitus: Effects on Cardiovascular and Renal Disease J. Clin. Endocrinol. Metab., February 1, 2003; 88(2): 516 - 523. [Full Text] [PDF]
|
|
|
|
|
|
M. F. Rousseau, O. Gurne, D. Duprez, W. Van Mieghem, A. Robert, S. Ahn, L. Galanti, J.-M. Ketelslegers, and Belgian RALES Investigators Beneficial neurohormonal profile of spironolactone in severe congestive heart failure: Results from the RALES neurohormonal substudy J. Am. Coll. Cardiol., November 6, 2002; 40(9): 1596 - 1601. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
M. Cicoira, L. Zanolla, A. Rossi, G. Golia, L. Franceschini, G. Brighetti, P. Marino, and P. Zardini Long-term, dose-dependent effects of spironolactone on left ventricular function and exercise tolerance in patients with chronic heart failure J. Am. Coll. Cardiol., July 17, 2002; 40(2): 304 - 310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Yamamoto, H. Yasue, Y. Mizuno, M. Yoshimura, H. Fujii, M. Nakayama, E. Harada, S. Nakamura, T. Ito, and H. Ogawa Aldosterone Is Produced From Ventricles in Patients With Essential Hypertension Hypertension, May 1, 2002; 39(5): 958 - 962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
S. Neumann, K. Huse, R. Semrau, A. Diegeler, R. Gebhardt, G. H. Buniatian, and G. H. Scholz Aldosterone and D-Glucose Stimulate the Proliferation of Human Cardiac Myofibroblasts In Vitro Hypertension, March 1, 2002; 39(3): 756 - 760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Gomez-Sanchez and E. P. Gomez-Sanchez Cardiac Steroidogenesis--New Sites of Synthesis, or Much Ado About Nothing? J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5118 - 5120. [Full Text] [PDF]
|
|
|
|
|
|
M. J. Young, C. D. Clyne, T. J. Cole, and J. W. Funder Cardiac Steroidogenesis in the Normal and Failing Heart J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5121 - 5126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Zannad, B. Dousset, and F. Alla Treatment of Congestive Heart Failure: Interfering the Aldosterone-Cardiac Extracellular Matrix Relationship Hypertension, November 1, 2001; 38(5): 1227 - 1232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Harada, M. Yoshimura, H. Yasue, O. Nakagawa, M. Nakagawa, M. Harada, Y. Mizuno, M. Nakayama, Y. Shimasaki, T. Ito, et al. Aldosterone Induces Angiotensin-Converting-Enzyme Gene Expression in Cultured Neonatal Rat Cardiocytes Circulation, July 10, 2001; 104(2): 137 - 139. [Abstract] [Full Text] [PDF]
|
|