title: Estrogen therapy, independent of timing, improves cardiac structure and function in oophorectomized mRen2.Lewis rats.
abstract: OBJECTIVE
  mRen2.Lewis rats exhibit exacerbated increases in blood pressure, left ventricular (LV) remodeling, and diastolic impairment after the loss of estrogens. In this same model, depletion of estrogens has marked effects on the cardiac biopterin profile concomitant with suppressed nitric oxide release. With respect to the establishment of overt systolic hypertension after oophorectomy (OVX), we assessed the effects of timing long-term 17β-estradiol (E2) therapy on myocardial function, myocardial structure, and the cardiac nitric oxide system.
  
  
  METHODS
  OVX (n = 24) or sham operation (Sham; n = 13) was performed in 4-week-old female mRen2.Lewis rats. After randomization, OVX rats received E2 immediately (OVX + E2-early; n = 7), E2 at 11 weeks of age (OVX + E2-late; n = 8), or no E2 at all (OVX; n = 9).
  
  
  RESULTS
  E2-early was associated with lower body weight, less hypertension-related cardiac remodeling, and decreased LV filling pressure compared with OVX rats without E2 supplementation. E2-late similarly attenuated the adverse effects of ovarian hormone loss on tissue Doppler-derived LV filling pressures and perivascular fibrosis, and significantly improved myocardial relaxation or mitral annular velocity (e'). Early and late exposures to E2 decreased dihydrobiopterin, but only E2-late yielded significant increases in cardiac nitrite concentrations.
  
  
  CONCLUSIONS
  Although there are some similarities between E2-early and E2-late treatments in relation to preservation of diastolic function and cardiac structure after OVX, the lusitropic potential of E2 is most consistent with late supplementation. The cardioprotective effects of E2-late are independent of blood pressure and may have occurred through regulation of cardiac biopterins and nitric oxide production.
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157-1009, USA.
authors.forename: Jewell A
authors.initials: JA
authors.lastname: Jessup
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: MacNamara
authors.forename: Tennille D
authors.initials: TD
authors.lastname: Presley
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Kim-Shapiro
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
authors.forename: Alex F
authors.initials: AF
authors.lastname: Chen
authors.forename: Leanne
authors.initials: L
authors.lastname: Groban
mesh_terms: D000818:Animals; D001708:Biopterins / Q000378:metabolism; D003971:Diastole / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D006321:Heart / Q000033:anatomy & histology / Q000187:drug effects* / Q000503:physiopathology; D006973:Hypertension / Q000150:complications / Q000517:prevention & control; D009206:Myocardium / Q000473:pathology; D009569:Nitric Oxide / Q000096:biosynthesis; D010052:Ovariectomy; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000517:prevention & control
chemical_list: D001708:Biopterins; D009569:Nitric Oxide; D004958:Estradiol