(Hypertension. 2006;48:994.)
© 2006 American Heart Association, Inc.
Original Articles |
From the Medizinische Klinik I (P.A.A.-L., K.H., A.S., J.B., T.Q., J.G., V.J., G.E., T.P.), University of Würzburg, Würzburg, Germany; Schering AG Berlin (K.-H.F., C.H.-H.), Berlin, Germany; and the Division of Cardiology (L.N.), University of Manchester, Manchester, United Kingdom.
Correspondence to Theo Pelzer, Medizinische Klinik I, University of Würzburg, Josef-Schneider Str 2, D-97080 Würzburg, Germany. E-mail pelzer_t{at}medizin.uni-wuerzburg.de
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 17ß-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 17ß-estradiol in ovariectomized animals after 8 weeks of continuous treatment. The beneficial role of 17ß-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 17ß-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.
Key Words: aldosterone estrogen medroxyprogesterone-acetate cardiac hypertrophy
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