title: Medroxyprogesterone acetate aggravates oxidative stress and left ventricular dysfunction in rats with chronic myocardial infarction.
abstract: The role of estrogens during myocardial ischemia has been extensively studied. However, effects of a standard hormone replacement therapy including 17β-estradiol (E2) combined with medroxyprogesterone acetate (MPA) have not been assessed, and this combination could have contributed to the negative outcomes of the clinical studies on hormone replacement. We hypothesized that adding MPA to an E2 treatment would aggravate chronic heart failure after experimental myocardial infarction (MI). To address this issue, we evaluated clinical signs of heart failure as well as left ventricular (LV) dysfunction and remodeling in ovariectomized rats subjected to chronic MI receiving E2 or E2 plus MPA. After eight weeks MI E2 showed no effects. Adding MPA to E2 aggravated LV remodeling and dysfunction as judged by increased heart weight, elevated myocyte cross-sectional areas, increased elevated left ventricle end diastolic pressure, and decreased LV fractional shortening. Impaired LV function in rats receiving MPA plus E2 was associated with increased cardiac reactive oxygen species generation and myocardial expression levels of NADPH oxidase subunits. These results support the interpretation that adding MPA to an E2 treatment complicates cardiovascular injury damage post-MI and therefore contributes to explain the adverse outcome of prospective clinical studies.
authors.affiliation: Medizinische Klinik I, University of Würzburg, Germany.
authors.forename: Paula Anahi
authors.initials: PA
authors.lastname: Arias-Loza
authors.forename: Kai
authors.initials: K
authors.lastname: Hu
authors.forename: Stefan
authors.initials: S
authors.lastname: Frantz
authors.forename: Charlotte
authors.initials: C
authors.lastname: Dienesch
authors.forename: Barbara
authors.initials: B
authors.lastname: Bayer
authors.forename: Rongxue
authors.initials: R
authors.lastname: Wu
authors.forename: Georg
authors.initials: G
authors.lastname: Ertl
authors.forename: Theo
authors.initials: T
authors.lastname: Pelzer
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D002908:Chronic Disease; D004562:Electrocardiography; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006651:Histocytochemistry; D017258:Medroxyprogesterone Acetate / Q000633:toxicity*; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D019255:NADPH Oxidases / Q000378:metabolism; D010052:Ovariectomy; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D017382:Reactive Oxygen Species; D004958:Estradiol; D017258:Medroxyprogesterone Acetate; D019255:NADPH Oxidases