Consequences of ethanol withdrawal on the vasculature and the systemic and local renin-angiotensin system (ras)

Abstract

The total or partial interruption of chronic ethanol consumption by alcoholics subjects can cause symptoms of varying intensity characterized, according to the International Classification of Diseases (ICD-10 - 10th edition; WHO) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV - 4th edition, American Psychiatric Association) as the Alcohol Withdrawal Syndrome (AWS). Signs and symptoms of the AWS include sweating, tremors, agitation, seizures, hallucinations, disorientation, delirium tremens, anxiety and hypertension. Some studies designed to investigate the effect of ethanol withdrawal on the cardiovascular function observed a transient increase in arterial pressure accompanied by vascular hyper-responsiveness. However, little is known about the mechanisms underlying this response. Abstinence to ethanol induces systemic and tissue oxidative stress. Lipid peroxidation induced by ethanol withdrawal was described in CNS structures (eg, hippocampus) and this response is associated with generation of reactive oxygen species (ROS), since elevated levels of superoxide anions (O2-) were detected in these tissues. Superoxide anion can interact with nitric oxide (NO) forming peroxynitrite (ONOO-) and this interaction may reduce NO bioavailability. Although ethanol withdrawal increases oxidative stress in the CNS, there is no data on the involvement of ROS in cardiovascular changes associated with ethanol withdrawal. Anxiety and stress associated with the AWS induce activation of the hypothalamic-pituitary-adrenal axis and the systemic renin-angiotensin system (RAS), since increased levels of renin and aldosterone were identified in abstinent patients. Angiotensin II (ANG II) is the active component of the RAS being produced systemically by the classic RAS. Currently it is known that RAS components are also present in the vasculature, indicating that vascular tissue is capable of producing ANG II locally. The hypothesis of this study is that ethanol withdrawal induces anxiety and RAS activation with consequent increase in ROS generation and decreased NO bioavailability. This response would alter vascular reactivity and increase blood pressure. Despite the existence of studies showing that chronic ethanol consumption induces activation of systemic RAS, oxidative stress and hypertension, there are no studies showing the detailed effects of ethanol withdrawal on the vasculature and the systemic and tissue RAS. Therefore, this study was designed to investigate the effects of ethanol withdrawal on vascular function and the systemic and local RAS. (AU)