We evaluated the possible mechanisms underlying the oxidative stress induced by ethanol withdrawal. With this purpose, we verified the role of AT₁ receptors in such response. Male Wistar rats were treated with ethanol 3%–9% (vol./vol.) for 21 days. Ethanol withdrawal was induced by abrupt discontinuation of the treatment. Experiments were performed 48 hours after ethanol discontinuation. Increased plasma levels of angiotensin II were detected after ethanol withdrawal. Losartan (10 mg/kg; p.o. gavage), a selective AT₁ receptor antagonist, impeded the increase in blood pressure induced by ethanol withdrawal. Increased lipoperoxidation and superoxide anion (O₂⁻) levels were detected in aortas after ethanol withdrawal, and losartan prevented these responses. Decreased hydrogen peroxide and nitrate/nitrite concentration were detected in aortas after ethanol withdrawal, and losartan prevented these effects. Nitrotyrosine immunostaining in the rat aorta was increased after ethanol withdrawal, and AT₁ blockade impeded this response. Increased expression of PKCδ and p47^phox was detected after ethanol withdrawal, and treatment with losartan prevented these responses. Our study provides novel evidence that ethanol withdrawal increases vascular oxidative stress and blood pressure through AT₁-dependent mechanisms. These findings highlight the importance of angiotensin II in ethanol withdrawal–induced increase in blood pressure and vascular oxidative damage.

我们评估了乙醇戒断所引起的氧化应激的潜在机制。为此，我们验证了AT ₁受体在这种反应中的作用。Wistar雄性大鼠用3％–9％（体积/体积）的乙醇处理21天。突然停止治疗可引起乙醇戒断。在乙醇中断后48小时进行实验。撤出乙醇后，血浆中血管紧张素II水平升高。选择性的AT ₁受体拮抗剂洛沙坦（10 mg / kg，口服）可阻止乙醇戒断引起的血压升高。脂质过氧化增加和超氧阴离子（O ₂ ^-撤出乙醇后在主动脉中检测到）的水平，而氯沙坦阻止了这些反应。撤除乙醇后，主动脉中检测到过氧化氢和硝酸盐/亚硝酸盐浓度降低，而氯沙坦阻止了这些作用。撤除乙醇后，大鼠主动脉中的硝基酪氨酸免疫染色增加，AT ₁阻滞阻止了该反应。撤除乙醇后，检测到PKCδ和p47 ^phox的表达增加，而氯沙坦治疗阻止了这些反应。我们的研究提供了新的证据，表明乙醇撤出可通过AT ₁增加血管氧化应激和血压依赖机制。这些发现凸显了血管紧张素II在乙醇戒断所引起的血压升高和血管氧化损伤中的重要性。