Ethanol Withdrawal Alters the Oxidative State of the Heart Through AT1-Dependent Mechanisms.

Abstract

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 21days. The cardiac effects of ethanol withdrawal were investigated 48h after abrupt discontinuation of ethanol. Some animals were orally treated with losartan (10mg/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.