title: Medroxyprogesterone acetate but not drospirenone ablates the protective function of 17 beta-estradiol in aldosterone salt-treated rats.
abstract: Controversial results obtained from human and animal studies on the prevention of heart disease by estrogens and progestins warrant a better understanding of nuclear hormone receptor function and interaction. To address this issue and taking into account that effects of synthetic progestins are not only referable to action through the progesterone receptor but may also be mediated by other steroid receptors, we characterized cardiovascular function and inflammatory gene expression in aldosterone salt-treated rats on long-term administration of 17beta-estradiol, medroxyprogesterone acetate, and drospirenone, a new progestogen exhibiting antimineralocorticoid activity. The complex pattern of cardiovascular injury in ovariectomized Wistar rats induced by chronic aldosterone infusion plus a high-salt diet was significantly attenuated in sham-ovariectomized rats and by coadministration of 17beta-estradiol in ovariectomized animals after 8 weeks of continuous treatment. The beneficial role of 17beta-estradiol on blood pressure, cardiac hypertrophy, vascular osteopontin expression, perivascular fibrosis, and impaired NO-dependent relaxation of isolated aortic rings was completely abrogated by coadministration of medroxyprogesterone acetate. In contrast, drospirenone was either neutral or additive to 17beta-estradiol in protecting against aldosterone salt-induced cardiovascular injury and inflammation. The current results support the hypothesis of complex interactions among estrogen, progesterone, glucocorticoid, androgen, and mineralocorticoid receptor signaling in cardiovascular injury and inflammation. Novel progestins, such as drospirenone, confer superior effects compared with medroxyprogesterone acetate in a model of aldosterone-induced heart disease because of its antimineralocorticoid properties.
authors.affiliation: Medizinische Klinik I, University of Würzburg, Josef-Schneider Str 2, D-97080 Würzburg, Germany.
authors.forename: Paula Anahi
authors.initials: PA
authors.lastname: Arias-Loza
authors.forename: Kai
authors.initials: K
authors.lastname: Hu
authors.forename: Andreas
authors.initials: A
authors.lastname: Schäfer
authors.forename: Johann
authors.initials: J
authors.lastname: Bauersachs
authors.forename: Thomas
authors.initials: T
authors.lastname: Quaschning
authors.forename: Jan
authors.initials: J
authors.lastname: Galle
authors.forename: Virginija
authors.initials: V
authors.lastname: Jazbutyte
authors.forename: Ludwig
authors.initials: L
authors.lastname: Neyses
authors.forename: Georg
authors.initials: G
authors.lastname: Ertl
authors.forename: Karl-Heinrich
authors.initials: KH
authors.lastname: Fritzemeier
authors.forename: Christa
authors.initials: C
authors.lastname: Hegele-Hartung
authors.forename: Theo
authors.initials: T
authors.lastname: Pelzer
mesh_terms: D000450:Aldosterone / Q000008:administration & dosage*; D000736:Androstenes / Q000008:administration & dosage* / Q000494:pharmacology*; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D002319:Cardiovascular System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D003094:Collagen / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism* / Q000502:physiology; D004965:Estrogen Antagonists / Q000008:administration & dosage* / Q000494:pharmacology*; D005260:Female; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage* / Q000494:pharmacology; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012492:Salts / Q000008:administration & dosage
chemical_list: D000736:Androstenes; D004965:Estrogen Antagonists; D000451:Mineralocorticoid Receptor Antagonists; D012492:Salts; D000450:Aldosterone; D004958:Estradiol; D003094:Collagen; D017258:Medroxyprogesterone Acetate; C035144:drospirenone