TY - JOUR
T1 - Distinct cardioprotective effects of 17β-estradiol and dehydroepiandrosterone on pressure overload-induced hypertrophy in ovariectomized female rats
AU - Tagashira, Hideaki
AU - Bhuiyan, Shenuarin
AU - Shioda, Norifumi
AU - Fukunaga, Koji
PY - 2011/12/1
Y1 - 2011/12/1
N2 - Objective: We recently reported decreased σ 1 receptor expression in the heart after abdominal aortic stenosis in bilateral ovariectomized rats. Here, we use ovariectomized female rats to investigate the distinct cardioprotective effects of 17β-estradiol (E 2) and dehydroepiandrosterone (DHEA) in pressure overload (PO)-induced cardiac dysfunction. Methods: E 2 (0.1 mg/kg) and DHEA (30 mg/kg) were administered to rats subcutaneously and orally, respectively, for 14 days starting 2 weeks after aortic banding. Results: Both E 2 and DHEA treatments significantly inhibited PO-induced increases both in heart weight/body weight ratio and lung weight/body weight ratios. Both E 2 and DHEA also ameliorated hypertrophy-induced impairment of left ventricular end-diastolic pressure, left ventricular-developed pressure, left ventricular contraction and relaxation (±dp/dt) rates, heart rate, and mean arterial blood pressure. Notably, DHEA but not E 2 administration rescued decreased PO-induced σ 1 receptor reduction in the heart. Coadministration with N,N-Dipropyl-2-[4-methoxy-3-(2-phenylethoxy) phenyl]-ethylamine monohydrochloride, an σ1 receptor antagonist, inhibited DHEA-induced amelioration of heart dysfunction without altering E 2-induced cardioprotection. Mechanistically, both E 2 and DHEA treatments significantly restored PO-induced decreases in protein kinase B (Akt) phosphorylation and Akt-mediated endothelial nitric oxide synthase (eNOS) phosphorylation (Ser1179). N,N-Dipropyl-2-[4-methoxy-3-(2-phenylethoxy) phenyl]-ethylamine monohydrochloride treatment totally abolished DHEA-induced Akt and eNOS phosphorylation without altering E 2-induced Akt-eNOS activation. Conclusions: Taken together, these results from an ovariectomized rat model of PO-induced cardiac dysfunction show that DHEA but not E 2 elicits a cardioprotective action through σ 1 receptor activation. DHEA-induced Akt-eNOS activation through σ 1 receptors is probably associated with its cardioprotective activity.
AB - Objective: We recently reported decreased σ 1 receptor expression in the heart after abdominal aortic stenosis in bilateral ovariectomized rats. Here, we use ovariectomized female rats to investigate the distinct cardioprotective effects of 17β-estradiol (E 2) and dehydroepiandrosterone (DHEA) in pressure overload (PO)-induced cardiac dysfunction. Methods: E 2 (0.1 mg/kg) and DHEA (30 mg/kg) were administered to rats subcutaneously and orally, respectively, for 14 days starting 2 weeks after aortic banding. Results: Both E 2 and DHEA treatments significantly inhibited PO-induced increases both in heart weight/body weight ratio and lung weight/body weight ratios. Both E 2 and DHEA also ameliorated hypertrophy-induced impairment of left ventricular end-diastolic pressure, left ventricular-developed pressure, left ventricular contraction and relaxation (±dp/dt) rates, heart rate, and mean arterial blood pressure. Notably, DHEA but not E 2 administration rescued decreased PO-induced σ 1 receptor reduction in the heart. Coadministration with N,N-Dipropyl-2-[4-methoxy-3-(2-phenylethoxy) phenyl]-ethylamine monohydrochloride, an σ1 receptor antagonist, inhibited DHEA-induced amelioration of heart dysfunction without altering E 2-induced cardioprotection. Mechanistically, both E 2 and DHEA treatments significantly restored PO-induced decreases in protein kinase B (Akt) phosphorylation and Akt-mediated endothelial nitric oxide synthase (eNOS) phosphorylation (Ser1179). N,N-Dipropyl-2-[4-methoxy-3-(2-phenylethoxy) phenyl]-ethylamine monohydrochloride treatment totally abolished DHEA-induced Akt and eNOS phosphorylation without altering E 2-induced Akt-eNOS activation. Conclusions: Taken together, these results from an ovariectomized rat model of PO-induced cardiac dysfunction show that DHEA but not E 2 elicits a cardioprotective action through σ 1 receptor activation. DHEA-induced Akt-eNOS activation through σ 1 receptors is probably associated with its cardioprotective activity.
KW - 17β-Estradiol
KW - Dehydroepiandrosterone
KW - Endothelial nitric oxide synthase
KW - Myocardial hypertrophy
KW - Protein kinase B
KW - σ Receptor
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U2 - 10.1097/gme.0b013e31821f915b
DO - 10.1097/gme.0b013e31821f915b
M3 - Article
C2 - 21844826
AN - SCOPUS:83055181391
VL - 18
SP - 1317
EP - 1326
JO - Menopause
JF - Menopause
SN - 1072-3714
IS - 12
ER -