Laboratório de Farmacologia, Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil.
Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil.
Alcohol Alcohol. 2020 Feb 7;55(1):3-10. doi: 10.1093/alcalc/agz101.
We investigated the cardiac effects of ethanol withdrawal and the possible role of AT1 receptors in such response.
Male Wistar rats were treated with increasing doses of ethanol (3 to 9%, vol./vol.) for 21 days. The cardiac effects of ethanol withdrawal were investigated 48 h after abrupt discontinuation of ethanol. Some animals were orally treated with losartan (10 mg/kg/day), a selective AT1 receptor antagonist.
Ethanol withdrawal did not affect serum levels of creatine kinase (CK)-MB. Losartan prevented ethanol withdrawal-induced increase in superoxide anion (O2•-) production in the left ventricle (LV). However, ethanol withdrawal did no alter the levels of thiobarbituric acid reactive substances (TBARS) or the expression of Nox1, Nox2 or Nox4 were found in the LV. Ethanol withdrawal reduced the concentration of hydrogen peroxide (H2O2) in the LV and this response was prevented by losartan. Ethanol withdrawal increased catalase activity in the LV and losartan attenuated this response. No changes on superoxide dismutase (SOD) activity or expression were detected in the LV during ethanol withdrawal. The expression of AT1, AT2 or angiotensin converting enzyme (ACE) was not affected by ethanol withdrawal. Similarly, no changes on the expression of ERK1/2, SAPK/JNK, COX-1 or COX-2 were found in the LV during ethanol withdrawal.
Ethanol withdrawal altered the cardiac oxidative state through AT1-dependent mechanisms. Our findings showed a role for angiotensin II/AT1 receptors in the initial steps of the cardiac effects induced by ethanol withdrawal.
我们研究了乙醇戒断对心脏的影响，以及 AT1 受体在此反应中的可能作用。
雄性 Wistar 大鼠连续 21 天接受递增剂量的乙醇（3%至 9%，体积/体积）治疗。在突然停止乙醇后 48 小时，研究了乙醇戒断的心脏效应。一些动物经口给予氯沙坦（10mg/kg/天），一种选择性 AT1 受体拮抗剂。
乙醇戒断未影响肌酸激酶（CK-MB）的血清水平。氯沙坦可预防乙醇戒断引起的左心室（LV）中超氧阴离子（O2•-）产生增加。然而，乙醇戒断并未改变 LV 中硫代巴比妥酸反应物质（TBARS）的水平或 Nox1、Nox2 或 Nox4 的表达。乙醇戒断降低了 LV 中过氧化氢（H2O2）的浓度，氯沙坦可预防这种反应。乙醇戒断增加了 LV 中的过氧化氢酶活性，氯沙坦减弱了这种反应。在乙醇戒断期间，LV 中的超氧化物歧化酶（SOD）活性或表达没有变化。AT1、AT2 或血管紧张素转换酶（ACE）的表达不受乙醇戒断的影响。同样，在乙醇戒断期间，LV 中未发现 ERK1/2、SAPK/JNK、COX-1 或 COX-2 的表达发生变化。
乙醇戒断通过 AT1 依赖机制改变了心脏的氧化状态。我们的研究结果表明，血管紧张素 II/AT1 受体在乙醇戒断引起的心脏效应的初始阶段发挥作用。
