Hormonal therapy with estradiol and drospirenone improves
endothelium-dependent vasodilation in the coronary bed of ovariectomized
spontaneously hypertensive rats |
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Authors: | MV Borgo ERG Claudio FB Silva WG Romero SA Gouvea MR Moysés RL Santos SA Almeida PL Podratz JB Graceli GR Abreu |
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Institution: | 1.Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal de Espírito Santo, Vitória, ES, Brasil;2.Departamento de Morfologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES, Brasil |
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Abstract: | Drospirenone (DRSP) is a progestin with anti-aldosterone properties and it reduces
blood pressure in hypertensive women. However, the effects of DRSP on
endothelium-dependent coronary vasodilation have not been evaluated. This study
investigated the effects of combined therapy with estrogen (E2) and DRSP on
endothelium-dependent vasodilation of the coronary bed of ovariectomized (OVX)
spontaneously hypertensive rats. Female spontaneously hypertensive rats (n=87) at 12
weeks of age were randomly divided into sham operated (Sham), OVX, OVX treated with
E2 (E2), and OVX treated with E2 and DRSP (E2+DRSP) groups. Hemodynamic parameters
were directly evaluated by catheter insertion into the femoral artery.
Endothelium-dependent vasodilation in response to bradykinin in the coronary arterial
bed was assessed using isolated hearts according to a modified Langendorff method.
Coronary protein expression of endothelial nitric oxide synthase and estrogen
receptor alpha (ER-α) was assessed by Western blotting. Histological slices of
coronary arteries were stained with hematoxylin and eosin, and morphometric
parameters were analyzed. Oxidative stress was assessed in situ by
dihydroethidium fluorescence. Ovariectomy increased systolic blood pressure, which
was only prevented by E2+DRSP treatment. Estrogen deficiency caused endothelial
dysfunction, which was prevented by both treatments. However, the vasodilator
response in the E2+DRSP group was significantly higher at the three highest
concentrations compared with the OVX group. Reduced ER-α expression in OVX rats was
restored by both treatments. Morphometric parameters and oxidative stress were
augmented by OVX and reduced by E2 and E2+DRSP treatments. Hormonal therapy with E2
and DRSP may be an important therapeutic option in the prevention of coronary heart
disease in hypertensive post-menopausal women. |
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Keywords: | Menopause Hypertension Hormone therapy Drospirenone Coronary reactivity |
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