title: The estrogen receptor-alpha agonist 16alpha-LE2 inhibits cardiac hypertrophy and improves hemodynamic function in estrogen-deficient spontaneously hypertensive rats.
abstract: OBJECTIVE
  Cardiac mass increases with age and with declining estradiol serum levels in postmenopausal women. Although the non-selective estrogen receptor-alpha and -beta agonist 17beta-estradiol attenuates cardiac hypertrophy in animal models and in observational studies, it remains unknown whether activation of a specific estrogen receptor subtype (ERalpha or ERbeta) 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 ERalpha agonist 16alpha-LE2 or 17beta-estradiol.
  
  
  RESULTS
  Long-term administration of 16alpha-LE2 or 17beta-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 16alpha-LE2 were abrogated by the ER antagonist ZM-182780. Improved left ventricular function upon 16alpha-LE2 treatment was also observed in cardiac MRI studies. In contrast to estradiol and 16alpha-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 ERalpha favorably affects cardiac hypertrophy, myocardial contractility, and gene expression in ovariectomized SHR. Further studies are required to determine whether activation ERbeta mediates redundant or divergent effects.
authors.affiliation: Department of Medicine, University of Würzburg, Josef-Schneider Str. 2, D-97080 Würzburg, Germany. pelzer_t@klinik.uni-wuerzburg.de
authors.forename: Theo
authors.initials: T
authors.lastname: Pelzer
authors.forename: Virginija
authors.initials: V
authors.lastname: Jazbutyte
authors.forename: Kai
authors.initials: K
authors.lastname: Hu
authors.forename: Stephan
authors.initials: S
authors.lastname: Segerer
authors.forename: Matthias
authors.initials: M
authors.lastname: Nahrendorf
authors.forename: Peter
authors.initials: P
authors.lastname: Nordbeck
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Bonz
authors.forename: Jenny
authors.initials: J
authors.lastname: Muck
authors.forename: Karl-Heinrich
authors.initials: KH
authors.lastname: Fritzemeier
authors.forename: Christa
authors.initials: C
authors.lastname: Hegele-Hartung
authors.forename: Georg
authors.initials: G
authors.lastname: Ertl
authors.forename: Ludwig
authors.initials: L
authors.lastname: Neyses
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D006332:Cardiomegaly / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists*; D005260:Female; D000077267:Fulvestrant; D015870:Gene Expression / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000378:metabolism / Q000473:pathology; D066298:In Vitro Techniques; D008279:Magnetic Resonance Imaging; D023421:Models, Animal; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018995:Myosin Heavy Chains / Q000378:metabolism; D009929:Organ Size; D010052:Ovariectomy; D010210:Papillary Muscles / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D013629:Tamoxifen / Q000378:metabolism / Q000627:therapeutic use; D024723:Ventricular Myosins / Q000378:metabolism
chemical_list: D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D013629:Tamoxifen; D000077267:Fulvestrant; D004958:Estradiol; D009320:Atrial Natriuretic Factor; D024723:Ventricular Myosins; D018995:Myosin Heavy Chains