Aging Reduces the Efficacy of Estrogen Substitution to Attenuate Cardiac Hypertrophy in Female Spontaneously Hypertensive Rats

Abstract

Abstract-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 17␤-estradiol (E2; 2 g/kg body weight per day) for 6 weeks (nϭ10/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 17␤-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. (Hypertension. 2006;48:579-586.)

Cardiovascular Changes During Maturation and Ageing in Male and Female Spontaneously Hypertensive Rats

“…Cardiac hypertrophy is 41,42 and in female hypertensive rats. 23,43,44 . Unlike LV chamber dilation that only occurred in the male SHR, aortic arch dilatation was a feature in both male and female SHRs.…”

Stimulation of cardiac apoptosis in ovariectomized hypertensive rats: potential role of the renin–angiotensin system

“…hypertrophy in female SHRs [35]. Our study has been performed in young animals and thus do not take the possibility of aging effects into account.…”

Ventilation and phrenic output following high cervical spinal hemisection in male vs. female rats

“…Prior reports of plasma progesterone and estradiol in rats are somewhat variable (Cameron et al, 2002;Blair and Mickelsen, 2006;Donadio et al, 2006;Jazbutyte et al, 2006;Bernuci et al, 2008). This variability may reflect differences in rat strain, the time of day and/or the particular estrous cycle phase during sampling (Freeman, 1994).…”