Abstract
Elevated circulating aldosterone level is associated with impaired cardiovascular function. As shown by RALES and EPHESUS clinical studies, aldosterone antagonists decrease total and cardiovascular mortality in heart failure and post-MI with left ventricular dysfunction. Aldosterone induces cardiac fibrosis in both experimental models and clinical conditions. Nevertheless, the pathophysiology of aldosterone-induced cardiac alterations remains in large part unclear. To resolve this issue we have explored the possibility that the heart may produce aldosterone. We found that there is in fact a myocardial production of the hormone which is regulated by the same physiological stimuli than in the adrenals. This local aldosterone production is increased in post-MI and is in part responsible for cardiac fibrosis. Then, transgenic mice that overexpress the terminal enzyme of aldosterone biosynthesis, aldosterone-synthase, AS, in the heart have been raised by gene targeting with the alpha-myosin heavy chain promoter. Aldosterone concentration was enhanced 1.7-fold in transgenic hearts with no evidences of either structural or functional myocardial alterations. In contrast, male transgenic mice displayed a major endothelium-independent alteration of the coronary vasodilatation. To conclude, a moderately increased local concentration in aldosterone results in a pronounced coronary dysfunction without other cardiac alterations, which is a newly identified effect of aldosterone. This aldosterone-induced decrease of coronary reserve may be a new risk factor for cardiovascular diseases.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Yusuf S, Reddy S, Ounpuu S et al. Global burden of cardiovascular diseases. Part II: variations in cardiovascular disease by specific ethnic groups and geographic regions and prevention strategies. Circulation 2001, 104, 2855–2864.
Swynghedauw B. Molecular mechanisms of myocardial remodeling. Physiol. Rev. 1999, 79, 215–262.
Swynghedauw B. Myocardial remodelling: pharmacological targets. Expert Opin. Invest. Drugs 2002, 11, 661–674.
Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N. Engl. J. Med. 1999, 341, 709–717.
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, 1309–21.
Delcayre C, Swynghedauw B. Molecular mechanisms of myocardial remodeling. The role of aldosterone. J. Mol. Cell. Cardiol. 2002, 34, 1577–84.
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, 125, 563–575.
Robert V, Silvestre JS, Charlemagne D, et al. Biological determinants of aldosterone-induced cardiac fibrosis in rat. Hypertension 1995, 26, 971–978.
Rocha R, Rudolph AE, Frierdich GE, et al. Aldosterone induces a vascular inflammatory phenotype in the rat heart. Am. J. Physiol. Heart Circ. Physiol. 2002, 283, H1802–H1810.
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.
Silvestre JS, Heymes C, Oubénaïssa A, et al. Activation of cardiac adosterone production in rat myocardial infarction: effect of angiotensin II blockade and role in cardiac fibrosis. Circulation 1999, 99, 2694–2701.
Young MJ, Clyne CD, Cole TJ, Funder JW. Cardiac steroidogenesis in the normal and failing heart. J. Clin. Endocrinol. Metab. 2001, 86, 5121–5126.
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, 3936–40.
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, 1284–91.
Mizuno Y, Yoshimura M, Yasue H, et al. Aldosterone production is activated in failing ventricle in humans. Circulation 2001, 103, 72–77.
Sun Y, Zhang J, Lu L, Chen SS, et al. Aldosterone-induced inflammation in the rat heart. Am. J. Pathol. 2002, 161, 1773–1781.
Gerling IC, Sun Y, Ahokas RA et al. Aldosteronism: an immunostimulatory state precedes proinflammatory/fibrogenic cardiac phenotype. Am. J. Physiol. Heart Circ. Physiol. 2003, 285, H813–21.
Heymes C, Garnier A, Fuchs S et al. Aldosterone-synthase overexpression in heart: a tool to explore aldosterone effects. Mol. Cell. Endocrinol. 2004, 217, 213–219.
Garnier A, Bendall JK, Fuchs S et al. Cardiac specific increase in aldosterone production induces coronary dysfunction in aldosterone synthase-transgenic mice. Circulation 2004, 110, 1819–1825.
White PC. Aldosterone: direct effects on and production by the heart. J Clin Endocrinol Metab 2003;88:2376–83.
Benitah JP, Vassort G. Aldosterone upregulates Ca(2+) current in adult rat cardiomyocytes. Circ Res. 1999;85:1139–45.
Farquharson CAJ, Struthers AD. Spironolactone increases nitric oxide bioactivity, improves endothelial vasodilator dysfunction, and suppresses vascular angiotensin I/angiotensin II conversion in patients with chronic heart failure. Circulation 2000;101:594–7.
Bauersachs J, Heck M, Fraccarollo D, et al. Addition of spironolactone to angiotensin-converting enzyme inhibition in heart failure improves endothelial vasomotor dysfunction: role of vascular superoxide anion formation and endothelial nitric oxide synthase expression. J Am Coll Cardiol. 2002;39:351–8.
Robert V, NV Thiem, SL Cheav, et al. Increased cardiac collagens (I) and (III) mRNAs in aldosterone-salt hypertension. Hypertension 1994; 24: 30–36.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Springer Science+Business Media, Inc.
About this paper
Cite this paper
Swynghedauw, B., Heymes, C., Delcayre, C. (2006). Cardiac Aldosterone Production: A Vascular Problem?. In: Frohlich, E.D., Re, R.N. (eds) The Local Cardiac Renin Angiotensin-Aldosterone System. Basic Science for the Cardiologist, vol 20. Springer, Boston, MA. https://doi.org/10.1007/0-387-27826-5_15
Download citation
DOI: https://doi.org/10.1007/0-387-27826-5_15
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-387-27825-4
Online ISBN: 978-0-387-27826-1
eBook Packages: MedicineMedicine (R0)