Menezes Laís Almeida, Endlich Patrick Wander, Lima Deiviany Santana Santos, Peluso A Augusto, de Almeida Simone Alves, Borgo Mariana Veronez, Santos Robson Augusto Souza, de Abreu Glaucia Rodrigues
Department of Physiological Sciences, Health Sciences Center, Federal University of Espírito Santo, Vitória 29043-900, Brazil.
Mucuri School of Medicine, Post-Graduate Program in Health Sciences, Federal University of the Jequitinhonha and Mucuri Valleys, Teófilo Otoni 39803-371, Brazil.
Int J Mol Sci. 2025 May 21;26(10):4930. doi: 10.3390/ijms26104930.
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) (OE), OVX and treated with E2 and drospirenone (OE + 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 (ATR), Ang II type-2 receptor (ATR), 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 OE, OE + DRSP, and MPA-treated groups, while the administration of the ATR 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 ATR or ACE2 between the groups, but the MPA group showed significantly increased levels of ATR and eNOS. We concluded that ovariectomy induced vascular dysfunction linked to RAS regulation, and both estrogen (E2) and progestins differentially restored these parameters.
肾素-血管紧张素系统（RAS）是负责控制心血管稳态的主要内分泌和组织成分，其可受雌激素水平调节。本研究调查了雌激素和孕激素激素治疗对去卵巢大鼠血管紧张素-（1-7）[Ang-（1-7）]介导的血管舒张的影响以及涉及RAS的可能机制。雌性Wistar大鼠分为以下几组：假手术组（SHAM）、去卵巢组（OVX）、去卵巢并用17β-雌二醇（E2）治疗组（OE）、去卵巢并用E2和屈螺酮治疗组（OE + DRSP）以及去卵巢并用甲羟孕酮（MPA）治疗组。通过灌胃进行激素治疗28天。在分离的主动脉环中评估对Ang-（1-7）的血管反应，并使用胸主动脉的蛋白质印迹法测定血管紧张素II（Ang II）1型受体（ATR）、Ang II 2型受体（ATR）、Ang-（1-7）受体（Mas）、血管紧张素转换酶2（ACE2）和内皮型一氧化氮合酶（eNOS）的蛋白水平。结果显示去卵巢导致血管反应性受损。Ang-（1-7）在OE、OE + DRSP和MPA治疗组中诱导血管舒张，而在OVX + MPA组中给予ATR拮抗剂（PD123319）或选择性Mas拮抗剂（A779）增加了Ang-（1-7）诱导的血管舒张程度。各组之间主动脉中ATR或ACE2水平无差异，但MPA组显示ATR和eNOS水平显著升高。我们得出结论，去卵巢诱导与RAS调节相关的血管功能障碍，雌激素（E2）和孕激素均可不同程度地恢复这些参数。
