Cardiac Effects of Aldosterone, the Bad, but Is There Also a Good?

  • Ludovic Bénard
  • Bernard Swynghedauw
  • Paul Milliez
  • Marie-Lory Ambroisine
  • Smail Messaoudi
  • Jane-Lise Samuel
  • Claude Delcayre
Conference paper


Several trials have demonstrated the important benefit of aldosterone, aldo, antagonists in patients with heart failure, HF, and the commonly accepted conclusion is that it is important to block aldo in every disease conditions. High doses of aldo generate myocardial fibrosis in the rat through pericoronary inflammatory reaction and necrosis. Low doses of aldo can be targeted in the myocardium by using a transgenic model of mice overexpressing aldo synthase, TGAS, in the cardiac tissue. In this model the normal cardiac content in aldo is enhanced by a factor of 1.7. TGAS mice have a normal cardiac function and no significant fibrosis.


Myocardial Fibrosis Diabetic Cardiomyopathy BKCa Channel Aldosterone Blockade Systolic Left Ventricle Dysfunction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Ambroisine ML, Favre J, Oliviero P, et al. Coronary dysfunction in transgenic mice involves the bkca channels of vascular smooth muscle cells. Circulation. 2007;116:2435–2443.PubMedCrossRefGoogle Scholar
  2. 2.
    Boudin S, Abel ED. Diabetic cardiomyopathy revisited. Circulation. 2007;115:3213–3223.CrossRefGoogle Scholar
  3. 3.
    Bridgham JT, Carroll SM, Thornton JW. Evolution of hormone-receptor complexity by molecular exploitation. Science. 2006;312:97–101.PubMedCrossRefGoogle Scholar
  4. 4.
    Brilla C, Matsubara LS, Weber KT. Anti-aldosterone treatment and the prevention of myocardial fibrosis in primary and secondary hyperaldosteronism. J Mol Cell Cardiol. 1993;l25:563–575.CrossRefGoogle Scholar
  5. 5.
    Connell JMC, Davies E. The new biology of aldosterone. J Endocrinol. 2005;186:1–20.PubMedCrossRefGoogle Scholar
  6. 6.
    Davies JI, Band M, Morris A, et al. Spironolactone impairs endothelial function and heart rate variability in patients with type 2 diabetes. Diabetologia. 2004;47:1687–1694.PubMedCrossRefGoogle Scholar
  7. 7.
    Garnier A, Bendall JK, Fuchs S, et al. Cardiac overexpression of aldosterone-synthase induces a major coronary vascular dysfunction in mice. Circulation. 2004;110:1819–1825.PubMedCrossRefGoogle Scholar
  8. 8.
    Ledoux J, Werner ME, Brayden JE, et al. Calcium-activated potassium channels and the regulation of vascular tone. Physiology (Bethesda). 2006;21:69–78.Google Scholar
  9. 9.
    Michel F, Ambroisine ML, Duriez M, et al. Aldosterone enhances ischemia-induced neovascularization through angiotensin II-dependent pathway. Circulation. 2004;109:1933–1937.PubMedCrossRefGoogle Scholar
  10. 10.
    Mizuno Y, Yoshimura M, Yasue H, et al. Aldosterone production is activated in failing ventricle in humans. Circulation. 2001;103:72–77.PubMedGoogle Scholar
  11. 11.
    Nagar D, Liu XT, Rosenfeld CR. Estrogen regulates (beta)1-subunit expression in Ca2+ activated-K channel in arteries from reproductive tissues. Am J Physiol Heart Circulation Physiol. 2005;289:H1417–1427.CrossRefGoogle Scholar
  12. 12.
    Orio P, Rojas P, Ferreira G, et al. New disguises for an old channel: MaxiK channel beta-subunits. News Physiol Sci. 2002;17:156–161.PubMedGoogle Scholar
  13. 13.
    Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348:1309–1321.PubMedCrossRefGoogle Scholar
  14. 14.
    Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999;341:709–717.PubMedCrossRefGoogle Scholar
  15. 15.
    Poornima IG, Parikh P, Shannon RP. Diabetic cardiomyopathy. The search for a unifying hypothesis. Circ Res. 2006;98:596–605.PubMedCrossRefGoogle Scholar
  16. 16.
    Robert V, Silvestre JS, Charlemagne D, et al. Biological determinants of aldosterone-induced cardiac fibrosis in rat. Hypertension. 1995;26:971–978.PubMedGoogle Scholar
  17. 17.
    Silvestre JS, Heymes C, Oubénaïssa A, et al. Activation of cardiac aldosterone production in rat myocardial infarction: effect of angiotensin II blockade and role in cardiac fibrosis. Circulation. 1999;99:2694–2701.PubMedGoogle Scholar
  18. 18.
    Silvestre JS, Robert V, Heymes C, et al. Myocardial production of aldosterone and corticosterone in the rat. Physiological regulation. J Biol Chem. 1998;273:4883–4891.PubMedCrossRefGoogle Scholar
  19. 19.
    Sun Y, Zhang J, Lu L, Chen SS, et al. Aldosterone-induced inflammation in the rat heart. Am J Pathol. 2002;161:1773–1781.PubMedCrossRefGoogle Scholar
  20. 20.
    Swaminathan K, Davies J, George J, et al. Spironolactone for poorly controlled hypertension in type 2 diabetes: conflicting effects on blood pressure, endothelial function, glycemic control and hormonal profiles. Diabetes. 2008;51:762–768.Google Scholar
  21. 21.
    Swynghedauw B. Nothing in medicine makes sense except in the light of evolution. A review. In: Pontarotti P, ed. Evolutionary Biology. From Concept to Application. Berlin: Springer-Verlag; 2008:197–208.Google Scholar
  22. 22.
    Tsybouleva N, Zhang L, Chen S, et al. Aldosterone, through novel signaling proteins, is a fundamental molecular bridge between the genetic defect and the cardiac phenotype of hypertrophic cardiomyopathy. Circulation. 2004;109:1284–1291.Google Scholar
  23. 23.
    Yoshimura M, Nakamura S, Ito T, et al. Expression of aldosterone synthase gene in failing human heart: quantitative analysis using modified real-time polymerase chain reaction. J Clin Endocrinol Metab. 2002;87:3936–3940.PubMedCrossRefGoogle Scholar
  24. 24.
    Zannad F, Alla F, Dousset B, et al. Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from the randomized aldactone evaluation study (RALES). Rales Investigators. Circulation. 2000;102:2700–2706.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Ludovic Bénard
    • 1
  • Bernard Swynghedauw
    • 1
  • Paul Milliez
    • 1
  • Marie-Lory Ambroisine
    • 1
  • Smail Messaoudi
    • 1
  • Jane-Lise Samuel
    • 1
  • Claude Delcayre
    • 1
  1. 1.INSERM U 127, Hôpital LariboisièreParis Cedex 10France

Personalised recommendations