Copyright © 2005, European Society of Cardiology
The estrogen receptor-
agonist 16-LE2 inhibits cardiac hypertrophy and improves hemodynamic function in estrogen-deficient spontaneously hypertensive rats
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-
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 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 agonist 16-LE2 or 17β-estradiol.
Methods and Results: Long-term administration of 16-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 -myosin heavy chain expression. The observed effects of E2 and 16-LE2 were abrogated by the ER antagonist ZM-182780. Improved left ventricular function upon 16-LE2 treatment was also observed in cardiac MRI studies. In contrast to estradiol and 16-LE2, tamoxifen inhibited cardiac hypertrophy but failed to increase -myosin heavy chain expression and cardiac output.
Conclusions: These results support the hypothesis that activation of ER 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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