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Cardiovascular Research 2005 67(4):604-612; doi:10.1016/j.cardiores.2005.04.035
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Copyright © 2005, European Society of Cardiology

The estrogen receptor-{alpha} agonist 16{alpha}-LE2 inhibits cardiac hypertrophy and improves hemodynamic function in estrogen-deficient spontaneously hypertensive rats

Theo Pelzera,*, Virginija Jazbutytea, Kai Hua, Stephan Segerera, Matthias Nahrendorfa, Peter Nordbecka, Andreas W. Bonza, Jenny Mucka, Karl-Heinrich Fritzemeierb, Christa Hegele-Hartungb, Georg Ertla and Ludwig Neysesc

aDepartment of Medicine, University of Würzburg, Josef-Schneider Str. 2, D-97080 Würzburg, Germany
bSchering AG Berlin / Germany
cDivision of Cardiology, University of Manchester United Kingdom

* Corresponding author. Tel.: +49 931 201 36112; fax: +49 931 201 36212. Email address: pelzer_t{at}klinik.uni-wuerzburg.de

Objective: Cardiac mass increases with age and with declining estradiol serum levels in postmenopausal women. Although the non-selective estrogen receptor-{alpha} and -β agonist 17β-estradiol attenuates cardiac hypertrophy in animal models and in observational studies, it remains unknown whether activation of a specific estrogen receptor subtype (ER{alpha} or ERβ) might give similar or divergent results. Therefore, we analyzed myocardial hypertrophy as well as cardiac function and gene expression in ovariectomized, spontaneously hypertensive rats (SHR) treated with the subtype-selective ER{alpha} agonist 16{alpha}-LE2 or 17β-estradiol.

Methods and Results: Long-term administration of 16{alpha}-LE2 or 17β-estradiol did not affect elevated blood pressure, but both agonists efficiently attenuated cardiac hypertrophy and increased cardiac output, left ventricular stroke volume, papillary muscle strip contractility, and cardiac {alpha}-myosin heavy chain expression. The observed effects of E2 and 16{alpha}-LE2 were abrogated by the ER antagonist ZM-182780. Improved left ventricular function upon 16{alpha}-LE2 treatment was also observed in cardiac MRI studies. In contrast to estradiol and 16{alpha}-LE2, tamoxifen inhibited cardiac hypertrophy but failed to increase {alpha}-myosin heavy chain expression and cardiac output.

Conclusions: These results support the hypothesis that activation of ER{alpha} favorably affects cardiac hypertrophy, myocardial contractility, and gene expression in ovariectomized SHR. Further studies are required to determine whether activation ERβ mediates redundant or divergent effects.

KEYWORDS Cardiac hypertrophy; Estrogen receptor; Spontaneously hypertensive rats

Time for primary review 28 days


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