Campos Cristina, Sartorio Carmem L, Casali Karina R, Fernandes Rafael O, Llesuy Susana, da Rosa Araujo Alex S, Belló-Klein Adriane, Rigatto Katya Vianna
*Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; †Instituto de Cardiologia do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; ‡Universidade de Buenos Aires, Buenos Aires, Argentina; §Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.
J Cardiovasc Pharmacol. 2014 Feb;63(2):144-51. doi: 10.1097/FJC.0000000000000034.
: This study was conducted to test the hypothesis that 17β-estradiol therapy improves redox balance by decreasing reactive oxygen species production and increasing nitric oxide (NO) bioavailability, favoring Akt pathway activation and resulting in a better autonomic vascular control. Ovariectomized female Wistar rats were divided into 4 groups: (1) vehicle (VL) and animals treated with a pellet of 17β-estradiol for 21 days; (2) low dose (LE; 0.05 mg); (3) medium dose (ME; 0.2 mg); and (4) high dose (HE; 0.5 mg). Arterial pressure and its sympathetic nervous system modulation were evaluated by spectral analysis. Nitric oxide synthase and NADPH oxidase (Nox) activities, H2O2 concentration, redox status (GSH/GSSG), protein expression of Trx-1 and p-Akt/Akt were evaluated in the aorta, whereas NO metabolites were measured in the serum. Estrogen-treated groups showed a significant decrease in arterial pressure and sympathetic vascular drive. Redox status was significantly improved and NADPH oxidase and H2O2 were decreased in all estrogen-treated groups. Estrogen also induced an enhancement in NO metabolites, nitric oxide synthase activity, and Akt phosphorylation. This study demonstrated that estrogen treatment to ovariectomized rats induced cardioprotection, which was evidenced by reduced blood pressure variability and vascular sympathetic drive. These effects were associated with an improved redox balance and Akt activation, resulting in an enhanced NO bioavailability.
17β-雌二醇疗法通过减少活性氧生成和增加一氧化氮（NO）生物利用度来改善氧化还原平衡，有利于Akt通路激活，从而实现更好的自主神经血管控制。将去卵巢的雌性Wistar大鼠分为4组：（1）载体组（VL）和接受17β-雌二醇丸剂治疗21天的动物；（2）低剂量组（LE；0.05 mg）；（3）中剂量组（ME；0.2 mg）；（4）高剂量组（HE；0.5 mg）。通过频谱分析评估动脉血压及其交感神经系统调节。在主动脉中评估一氧化氮合酶和NADPH氧化酶（Nox）活性、H2O2浓度、氧化还原状态（GSH/GSSG）、Trx-1和p-Akt/Akt的蛋白表达，而在血清中测量NO代谢产物。雌激素治疗组的动脉血压和交感神经血管驱动力显著降低。所有雌激素治疗组的氧化还原状态均显著改善，NADPH氧化酶和H2O2减少。雌激素还诱导NO代谢产物、一氧化氮合酶活性和Akt磷酸化增强。本研究表明，对去卵巢大鼠进行雌激素治疗可诱导心脏保护作用，这表现为血压变异性和血管交感神经驱动力降低。这些作用与氧化还原平衡改善和Akt激活有关，从而提高了NO生物利用度。
