Key result
Estrogen and progestins differentially restore vascular function in ovariectomized rats via RAS regulation.
Why the study?
The renin-angiotensin system controls cardiovascular homeostasis and can be modulated by estrogen, prompting investigation into the effects of estrogen and progestins on Ang-(1-7)-mediated vasodilation in ovariectomized rats.
Does hormone replacement treatment with estrogen and progestins improve Ang-(1-7)-mediated vasodilation in ovariectomized rats?
Does hormone replacement treatment with estrogen and progestins improve Ang-(1-7)-mediated vasodilation in ovariectomized rats?
Hormone replacement therapy with 17β-estradiol and progestins prevents ovariectomy-induced vascular dysfunction by restoring Ang-(1-7)-mediated vasodilation, highlighting potential cardiovascular protection mechanisms of these agents.
Preclinical data only; leaves open whether estrogen-progestin combinations preserve Ang-(1-7) vasodilation in postmenopausal women.
The renin–angiotensin system (RAS) is the main endocrine and tissular component responsible for controlling cardiovascular homeostasis, which can be modulated by estrogen levels. This study investigated the effects of hormone treatments with estrogen and progestins on angiotensin-(1-7)-mediated [Ang-(1-7)] vasodilation in ovariectomized rats and the possible mechanisms involving the RAS. Female Wistar rats were divided into the following groups: sham (SHAM), ovariectomized (OVX), OVX and treated with 17β-estradiol (E2) (OE2), OVX and treated with E2 and drospirenone (OE2 + DRSP), and OVX and treated with medroxyprogesterone (MPA). Hormonal treatment was delivered via gavage for 28 days. Vascular responses to Ang-(1-7) were assessed in isolated aortic rings, and a Western blot of the thoracic aorta was used to determine the protein levels of angiotensin II (Ang II) type-1 receptor (AT1R), Ang II type-2 receptor (AT2R), Ang-(1-7) receptor (Mas), angiotensin-converting enzyme 2 (ACE2), and endothelial nitric oxide synthase (eNOS). The results showed impaired vascular reactivity caused by ovariectomy. Ang-(1-7) induced vasodilation in the OE2, OE2 + DRSP, and MPA-treated groups, while the administration of the AT2R antagonist (PD123319) or the selective Mas antagonist (A779) increased the extent of vasorelaxation induced by Ang-(1-7) in the OVX + MPA group. There were no differences in the aortic levels of AT1R or ACE2 between the groups, but the MPA group showed significantly increased levels of AT2R and eNOS. We concluded that ovariectomy induced vascular dysfunction linked to RAS regulation, and both estrogen (E2) and progestins differentially restored these parameters.
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Menezes et al. (2025) studied Ovariectomy-induced vascular dysfunction. 17β-estradiol (E2), drospirenone (DRSP), and medroxyprogesterone acetate (MPA) vs. Vehicle (OVX and SHAM groups) was evaluated on Ang-(1-7)-mediated vasodilation in isolated aortic rings. Treatment with 17β-estradiol alone or combined with drospirenone or medroxyprogesterone prevented the impairment of Ang-(1-7)-mediated vasodilation in the aorta of ovariectomized rats.
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