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(Hypertension. 2007;50:432.)
© 2007 American Heart Association, Inc.

Original Articles

Both Estrogen Receptor Subtypes, and ß, Attenuate Cardiovascular Remodeling in Aldosterone Salt–Treated Rats

Paula-Anahi Arias-Loza; Kai Hu; Charlotte Dienesch; Anna Maria Mehlich; Simone König; Virginia Jazbutyte; Ludwig Neyses; Christa Hegele-Hartung; Karl Heinrich Fritzemeier; Theo Pelzer

From the Medizinische Klinik I (P-A.A.-L., K.H., C.D., V.J., T.P.), University of Würzburg, Würzburg, Germany; Integrated Functional Genomics (A.M.M., S.K.), IZKF University of Münster, Münster, Germany; Division of Cardiology (L.N.), University of Manchester, Manchester, United Kingdom; and Schering AG (C.H-H., K.H.F.), Berlin, Germany.

Experimental and population-based studies indicate that female gender and estrogens protect the cardiovascular system against aldosterone-induced injury. Understanding the function of estrogens in heart disease requires more precise information on the role of both estrogen receptor (ER) subtypes, ER and ERß. Therefore, we determined whether selective activation of ER or of ERß would confer redundant, specific, or opposing effects on cardiovascular remodeling in aldosterone salt–treated rats. The ER agonist 16-LE2, the ERß agonist 8ß-VE2, and the nonselective estrogen receptor agonist 17ß-estradiol lowered elevated blood pressure, cardiac mass, and cardiac myocyte cross-sectional areas, as well as increased perivascular collagen accumulation and vascular osteopontin expression in ovariectomized rats receiving chronic aldosterone infusion plus a high-salt diet for 8 weeks. Uterus atrophy was prevented by 16-LE2 and 17ß-estradiol but not by 8ß-VE2. Cardiac proteome analyses by 2D gel electrophoresis, mass spectrometry, and peptide sequencing identified specific subsets of proteins involved in cardiac contractility, energy metabolism, cellular stress response and extracellular matrix formation that were regulated in opposite directions by aldosterone salt treatment and by different estrogen receptor agonists. We conclude that activation of either ER or ERß protects the cardiovascular system against the detrimental effects of aldosterone salt treatment and confers redundant, as well as specific, effects on cardiac protein expression. Nonfeminizing ERß agonists such as 8ß-VE2 have a therapeutic potential in the treatment of hypertensive heart disease.

Key Words: aldosterone • estrogen • proteomics • hypertrophy • inflammation

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