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.
Highlights
Coronary heart disease (CHD) is a major cause of morbidity and mortality worldwide [1], and hypertension is established as one of the main risk factors for the development of CHD [2]
Aging and decreased circulating estrogen (E2) levels are accompanied by increased blood pressure (BP), which contributes to a greater prevalence of hypertension and an increased prevalence of CHD during the post-menopausal period [3], suggesting a protective role for E2
At the time of ovariectomy, the rats were randomly divided into 4 groups as follows (n=87): sham control (Sham); OVX; OVX treated with estrogen (E2), and OVX treated with estrogen plus DRSP (E2+DRSP)
Summary
Coronary heart disease (CHD) is a major cause of morbidity and mortality worldwide [1], and hypertension is established as one of the main risk factors for the development of CHD [2]. Aging and decreased circulating estrogen (E2) levels are accompanied by increased BP, which contributes to a greater prevalence of hypertension and an increased prevalence of CHD during the post-menopausal period [3], suggesting a protective role for E2. Experimental studies analyzing the effects of estrogen replacement therapy in ovariectomized (OVX) rats have demonstrated many beneficial effects on the cardiovascular system. These beneficial effects include the capacity to lower BP in normotensive and hypertensive rats [4,5,6], reduce oxidative stress [4], prevent endothelial dysfunction, improve endothelium-dependent coronary vascular reactivity, and protect against vascular remodeling in early-stage hypertensive rats [7,8].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Brazilian Journal of Medical and Biological Research
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
