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Differences Between Cardiac and Arterial Fibrosis and Stiffness in Aldosterone-Salt Rats: Effect of Eplerenone

INSERM U572 Paris, France

Nathalie Mercier

INSERM U684 Vandoeuvre-les-Nancy, France

Carlos Labat

INSERM U684 Vandoeuvre-les-Nancy, France

Athanase Benetos

INSERM U684 Vandoeuvre-les-Nancy, France

Michel E Safar

The Diagnosis Center, Hôtel-Dieu Hospital, Paris, France, michel.safar{at}htd.aphp.fr

Claude Delcayre

INSERM U572 Paris, France

Patrick Lacolley

INSERM U684 Vandoeuvre-les-Nancy, France

Background. Previous experiments have studied separately the development of either cardiac or aortic fibrosis and stiffness in aldosterone (Aldo)-salt hypertensive rats. Our aim was to determine in vivo the effects of Aldo and the Aldo receptor antagonist eplerenone (Epl) on simultaneous changes in cardiac and arterial structure and function and their interactions.

Methods and Results. Aldo was administered in uninephrectomised Sprague-Dawley rats receiving a high-salt diet from 8 to 12 weeks of age. Three groups of Aldo-salt rats were treated with 1 to 100 mg/kg^-1. d^-1 Epl by gavage. Arterial elasticity was measured by elastic modulus (Einc)-wall stress curves using medial cross-sectional area (MCSA). The cardiac and arterial walls were analysed by histomorphometry (elastin and collagen), immunohistochemistry (EIIIA fibronectin, Fn), and Northern blot (collagens I and III). Aldo caused increased systolic blood pressure (SBP), carotid Einc, MCSA, and EIIIA Fn with no change in wall stress or elastin and collagen densities. No difference in collagen mRNA levels was detected between groups. During the same period, cardiac mass and collagen mRNA and protein levels increased markedly in the myocardial tissue. Epl normalised collagen in the myocardium, Eincwall stress curves, MCSA, and EIIIA Fn in Aldo rats. These dose-dependent effects were not accompanied by a consistent reduction in SBP and cardiac mass.

Conclusions. In exogenous hyperaldosteronism in the rat, Aldo causes independently myocardial collagen and arterial Fn accumulation, the latter being responsible for increased intrinsic carotid stiffness. Epl prevents both cardiac and arterial effects but does not reduce consistently SBP.

Key Words: Arteries • Hypertension • Elasticity • Pharmacology

References

• Brilla CG, Pick R., Tan LB et al. Remodelling of The Rat right and left ventricles in experimental hypertension. Circ Res
• Robert V., Van Thiem N., Cheav Sl et al. Increased cardiac types I and III collagen mRNAs in aldosterone-salt hypertension. Hypertension 1994;24:30-6.[Abstract/Free Full Text]
• Young M., Fullerton M., Dilley R. et al. Mineralocorticoids, hypertension and cardiac fibrosis. J Clin Invest 1994; 93:2578-83.[Web of Science][Medline] [Order article via Infotrieve]
• Brilla CG, Matsubara LS, Weber KT Anti-aldosterone treatment and the prevention of myocardial fibrosis in primary and secondary hyperaldosteronism. J Mol Cell Cardiol 1993;25:563-75.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Robert V., Silvestre JS, Charlemagne D. et al. Biological determinants of aldosterone-induced cardiac fibrosis in rats. Hypertension 1995;26:971-8.[Abstract/Free Full Text]
• Lombes M., Oblin ME, Gasc JM et al. Immunohistochemical and biochemical evidence of a cardiovascular mineralocorticoid receptor. Circ Res 1992;71:503-10.[Abstract/Free Full Text]
• Takeda Y., Miyamori I., Yoneda T. et al. Regulation of aldosterone synthase in human vascular endothelial cells by angiotensin II and adrenocorticotropin. J Clin Endocrinol Metab 1996;81:2797-800.[Abstract/Free Full Text]
• Hatakeyama H., Miyamori I., Fujita T. et al. Vascular aldosterone. Biosynthesis and a link to angiotensin II-induced hypertrophy of vascular smooth muscle cells. J Biol Chem 1994;269:24316-20.[Abstract/Free Full Text]
• Weber KT, Brilla CG, Campbell SE et al. Myocardial fibrosis: role of angiotensin II and aldosterone. Basic Res Cardiol 1993;88 (Suppl 1):107-24.[Web of Science][Medline] [Order article via Infotrieve]
• Silvestre JS, Robert V., Heymes C. et al. Myocardial production of aldosterone and corticosterone in the rat. Physiological regulation. J Biol Chem 1998;273:4883-91.[Abstract/Free Full Text]
• Lacolley P., Safar ME, Lucet B. et al. Prevention of aortic and cardiac fibrosis by spironolactone in old normotensive rats. J Am Coll Cardiol 2001;37:662-7.[Abstract/Free Full Text]
• Benetos A., Lacolley P., Safar ME Prevention of aortic fibrosis by spironolactone in spontaneously hypertensive rats (SHRs). Arterioscler Thromb Vasc Biol 1997;17:1152-6.[Abstract/Free Full Text]
• Lacolley P., Labat C., Pujol A. et al. Increased carotid wall elastic modulus and fibronectin in aldosterone-salt treated rats - effects of eplerenone. Circulation 2002;106:2848-53.[Abstract/Free Full Text]
• Swynghedauw B., Besse S., Assayag P. et al. Molecular and cellular biology of the senescent hypertrophied and failing heart. Am J Cardiol 1995;76:2D-7D.[CrossRef][Medline] [Order article via Infotrieve]
• Bezie Y., Lamazier J-M D., Laurent S. et al. Fibronectine expression and aortic wall elastic modulus in spontaneously hypertensive rats. Arterioscler Thromb Vasc Biol 1998; 18:1027-34.[Abstract/Free Full Text]
• Robert V., Heymes C., Silvestre JS et al. Angiotensin AT1 receptor subtype as a cardiac target of aldosterone: role in aldosterone-salt-induced fibrosis. Hypertension 1999;33:981-6.[Abstract/Free Full Text]
• Lal A., Veinot JP, Leenen FH Prevention of high salt dietinduced cardiac hypertrophy and fibrosis by spironolactone. Am J Hypertens 2003;16:319-23.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Ramirez-Gil JF, Delcayre C., Robert V. et al. In vivo left ventricular function and collagen expression in aldosterone/salt-induced hypertension. J Cardiovasc Pharmacol 1998;32:927-34.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Pitt B., Williams G., Remme W. et al. The EPHESUS trial: eplerenone in patients with heart failure due to systolic dysfunction complicating acute myocardial infarction. Eplerenone Post-AMI Heart Failure Efficacy and Survival Study. Cardiovasc Drugs Ther 2001;15:79-87.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Menard J. The 45-year story of the development of an anti-aldosterone more specific than spironolactone. Mol Cell Endocrinol 2004;217:45-52.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Fraccarollo D., Galuppo P., Hildemann S. et al. 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 2003;42:1666-73.[Abstract/Free Full Text]
• Nishikimi T., Horio T., Sasaki T. et al. Cardiac production and secretion of adrenomedullin are increased in heart failure. Hypertension 1997;30:1369-75.[Abstract/Free Full Text]
• Waldstein SS, Arcilla RA Measurement of hepatic blood flow by clearance methods; a review and a theoretical basis for a new noncatheterization method. Am J Dig Dis 1958;3:137-58.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Weiss YA, Safar ME, Lehner JP et al. (+)-Propranolol clearance, an estimation of hepatic blood flow in man. Br J Clin Pharmacol 1978;5:457-60.[Web of Science][Medline] [Order article via Infotrieve]
• Gildner CD, Lerner AL, Hocking DC Fibronectin matrix polymerization increases tensile strength of model tissue. Am J Physiol Heart Circ Physiol 2004;287:H46-H53.[Abstract/Free Full Text]
• Tsukamoto Y., Helsel WE, Wahl SM Macrophage production of fibronectin, a chemoattractant for fibroblasts. J Immunol 1981;127:673-8.[Abstract]
• Katayama K., Armendariz-Borunda J., Raghow R. et al. A pentapeptide from type I procollagen promotes extracellular matrix production. J Biol Chem 1993;268:9941-4.[Abstract/Free Full Text]
• Contard F., Koteliansky V., Marotte F. et al. Specific alterations in the distribution of extracellular matrix components within rat myocardium during the development of pressure overload. Lab Invest 1991;64:65-75.[Web of Science][Medline] [Order article via Infotrieve]
• Nishizaka MK, Zaman MA, Green SA et al. Impaired endothelium-dependent flow-mediated vasodilation in hypertensive subjects with hyperaldosteronism. Circulation 2004;109:2857-61.[Abstract/Free Full Text]
• Garnier A., Bendall JK, Fuchs S. et al. Cardiac specific increase in aldosterone production induces coronary dysfunction in aldosterone synthase-transgenic mice. Circulation 2004;110:1819-25.[Abstract/Free Full Text]
• Nichols WW, O'Rourke MF, Avolio AP et al. Effects of age on ventricular-vascular coupling. Am J Cardiol 1985;55:1179-84.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Safar ME, Cattan V., Lacolley P. et al. Aldosterone synthase gene polymorphism, stroke volume and age-related changes in aortic pulse wave velocity in subjects with hypertension. J Hypertens 2005;23:1159-66.[Web of Science][Medline] [Order article via Infotrieve]
• Blasi ER, Rocha R., Rudolph AE et al. Aldosterone/salt induces renal inflammation and fibrosis in hypertensive rats. Kidney Int 2003;63:1791-800.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Wojciechowska W., Staessen JA, Stolarz K. et al. European Project on Genes in Hypertension (EPOGH) Investigators. Association of peripheral and central arterial wave reflections with the CYP11B2 -344C allele and sodium excretion. J Hypertens 2004;22:2311-19.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Milliez P., Girerd X., Plouin PF et al. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol 2005;45:1243-8.[Abstract/Free Full Text]
• London GM, Pannier B., Guerin AP et al. Cardiac hypertrophy, aortic compliance, peripheral resistance, and wave reflection in end-stage renal disease. Comparative effects of ACE inhibition and calcium channel blockade. Circulation 1994;90:2786-96.[Abstract/Free Full Text]

Journal of Renin-Angiotensin-Aldosterone System, Vol. 7, No. 1, 31-39 (2006)
DOI: 10.3317/jraas.2006.004


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