title: Effects of estrogen on cardiovascular injury in ovariectomized female DahlS.Z-Lepr(fa)/Lepr(fa) rats as a new animal model of metabolic syndrome.
abstract: Although recent clinical trials have found an increased incidence of cardiovascular disease in women on estrogen replacement therapy, the underlying mechanism remains unclear. We have recently characterized DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, derived from a cross between Dahl salt-sensitive and Zucker rats, as a new animal model of metabolic syndrome. We have now examined the effects of estrogen replacement on cardiac pathophysiology in ovariectomized female DS/obese (Ovx-DS/obese) rats. Animals subjected to ovariectomy at 7 weeks of age were implanted subcutaneously with a 60-day release pellet containing 0.5 mg of 17β-estradiol (E(2)) or placebo at 8 weeks. Age-matched female homozygous lean littermates (DahlS.Z-Lepr(+)/Lepr(+) or DS/lean rats) of DS/obese rats served as controls. Animals were maintained on a normal diet and were subjected to echocardiography followed by various pathological analyses at 13 weeks of age. Ovx-DS/obese rats manifested hypertension at 7 weeks of age and thereafter and showed left ventricular (LV) fibrosis and diastolic dysfunction at 13 weeks. Treatment with E(2) attenuated hypertension in Ovx-DS/obese rats but had no effect on blood pressure in ovariectomized female DS/lean (Ovx-DS/lean) rats. E(2) treatment exacerbated LV fibrosis and diastolic dysfunction, as well as further increased cardiac oxidative stress and inflammation in Ovx-DS/obese rats, and it elicited similar effects in Ovx-DS/lean rats. E(2) reduced food intake, body weight, and visceral fat content in both Ovx-DS/obese and Ovx-DS/lean rats. E(2) treatment attenuated hypertension and obesity but exacerbated LV fibrosis and diastolic dysfunction in Ovx-DS/obese rats, with these latter effects being associated with increased cardiac oxidative stress and inflammation.
authors.affiliation: Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Tamayo
authors.initials: T
authors.lastname: Murase
authors.forename: Takuya
authors.initials: T
authors.lastname: Hattori
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ohtake
authors.forename: Chieko
authors.initials: C
authors.lastname: Nakashima
authors.forename: Miwa
authors.initials: M
authors.lastname: Takatsu
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.forename: Kohzo
authors.initials: K
authors.lastname: Nagata
mesh_terms: D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D004452:Echocardiography; D004958:Estradiol / Q000627:therapeutic use*; D004967:Estrogens / Q000627:therapeutic use; D005260:Female; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D024821:Metabolic Syndrome / Q000150:complications / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects; D010052:Ovariectomy / Q000009:adverse effects*; D051381:Rats; D020303:Rats, Inbred Dahl; D011924:Rats, Zucker; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control*
chemical_list: D004967:Estrogens; D004958:Estradiol