Ethanol withdrawal increases blood pressure and vascular oxidative stress: a role for angiotensin type 1 receptors

Abstract

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 p47phox 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.