title: Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats.
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.
authors.affiliation: Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal de Espírito Santo, Vitória, ES, Brasil.
authors.forename: M V
authors.initials: MV
authors.lastname: Borgo
authors.affiliation: Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal de Espírito Santo, Vitória, ES, Brasil.
authors.forename: E R G
authors.initials: ER
authors.lastname: Claudio
authors.affiliation: Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal de Espírito Santo, Vitória, ES, Brasil.
authors.forename: F B
authors.initials: FB
authors.lastname: Silva
authors.affiliation: Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal de Espírito Santo, Vitória, ES, Brasil.
authors.forename: W G
authors.initials: WG
authors.lastname: Romero
authors.affiliation: Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal de Espírito Santo, Vitória, ES, Brasil.
authors.forename: S A
authors.initials: SA
authors.lastname: Gouvea
authors.affiliation: Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal de Espírito Santo, Vitória, ES, Brasil.
authors.forename: M R
authors.initials: MR
authors.lastname: Moysés
authors.affiliation: Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal de Espírito Santo, Vitória, ES, Brasil.
authors.forename: R L
authors.initials: RL
authors.lastname: Santos
authors.affiliation: Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal de Espírito Santo, Vitória, ES, Brasil.
authors.forename: S A
authors.initials: SA
authors.lastname: Almeida
authors.affiliation: Departamento de Morfologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES, Brasil.
authors.forename: P L
authors.initials: PL
authors.lastname: Podratz
authors.affiliation: Departamento de Morfologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES, Brasil.
authors.forename: J B
authors.initials: JB
authors.lastname: Graceli
authors.affiliation: Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal de Espírito Santo, Vitória, ES, Brasil.
authors.forename: G R
authors.initials: GR
authors.lastname: Abreu
mesh_terms: D000736:Androstenes / Q000008:administration & dosage*; D000818:Animals; D015153:Blotting, Western; D001920:Bradykinin / Q000494:pharmacology; D003131:Combined Modality Therapy; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects*; D004958:Estradiol / Q000008:administration & dosage*; D047628:Estrogen Receptor alpha / Q000187:drug effects; D004967:Estrogens / Q000008:administration & dosage; D004996:Ethidium / Q000031:analogs & derivatives; D005260:Female; D005263:Femoral Artery; D006439:Hemodynamics; D020249:Hormone Replacement Therapy / Q000379:methods*; D006973:Hypertension / Q000188:drug therapy*; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects; D010052:Ovariectomy; D018384:Oxidative Stress / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000736:Androstenes; D047628:Estrogen Receptor alpha; D004967:Estrogens; D000451:Mineralocorticoid Receptor Antagonists; D014665:Vasodilator Agents; C067883:dihydroethidium; D004958:Estradiol; D052250:Nitric Oxide Synthase Type III; D004996:Ethidium; C035144:drospirenone; D001920:Bradykinin