Published online before print August 28, 2006, doi: 10.1161/01.HYP.0000240053.48517.c7
(Hypertension. 2006;48:579.)
© 2006 American Heart Association, Inc.
Original Articles |
Aging Reduces the Efficacy of Estrogen Substitution to Attenuate Cardiac Hypertrophy in Female Spontaneously Hypertensive Rats
From the Department of Medicine (V.J., K.H., S.K.G.M., G.E., T.P.), University of Würzburg, Würzburg, Germany; Pharmaceutical and Medicinal Chemistry (P.K., E.B., R.W.H.), Saarland University, Saarland, Germany; Schering AG (K.-H.F., K.P., C.H.-H.), Berlin, Germany; and the Division of Cardiology (L.N.), University of Manchester, Manchester, United Kingdom.
Correspondence to Theo Pelzer, Department of Medicine, University of Würzburg, Josef-Schneider Str 2, D-97080 Würzburg, Germany. E-mail pelzer_t{at}klinik.uni-wuerzburg.de
Clinical trials failed to show a beneficial effect of postmenopausal hormone replacement therapy, whereas experimental studies in young animals reported a protective function of estrogen replacement in cardiovascular disease. Because these diverging results could in part be explained by aging effects, we compared the efficacy of estrogen substitution to modulate cardiac hypertrophy and cardiac gene expression among young (age 3 months) and senescent (age 24 months) spontaneously hypertensive rats (SHRs), which were sham operated or ovariectomized and injected with placebo or identical doses of 17ß-estradiol (E2; 2 µg/kg body weight per day) for 6 weeks (n=10/group). Blood pressure was comparable among sham-operated senescent and young SHRs and not altered by ovariectomy or E2 treatment among young or among senescent rats. Estrogen substitution inhibited uterus atrophy and gain of body weight in young and senescent ovariectomized SHRs, but cardiac hypertrophy was attenuated only in young rats. Cardiac estrogen receptor-
expression was lower in intact and in ovariectomized senescent compared with young SHRs and increased with estradiol substitution in aged rats. Plasma estradiol and estrone levels were lower not only in sham-operated but surprisingly also in E2-substituted senescent SHRs and associated with a reduction of hepatic 17ß-hydroxysteroid dehydrogenase type 1 enzyme activity, which converts weak (ie, estrone) into potent estrogens, such as E2. Aging attenuates the antihypertrophic effect of estradiol in female SHRs and is associated with profound alterations in cardiac estrogen receptor- expression and estradiol metabolism. These observations contribute to explain the lower efficiency of estrogen substitution in senescent SHRs.
Key Words: estrogen receptors • cardiac hypertrophy • aging • hypertension
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