title: Ethanol withdrawal increases oxidative stress and reduces nitric oxide bioavailability in the vasculature of rats.
abstract: We analyzed the effects of ethanol withdrawal on the vascular and systemic renin-angiotensin system (RAS) and vascular oxidative stress. Male Wistar rats were treated with ethanol 3-9% (v/v) for a period of 21 days. Ethanol withdrawal was induced by abrupt discontinuation of the treatment. Experiments were performed 48 h after ethanol discontinuation. Rats from the ethanol withdrawal group showed decreased exploration of the open arms of the elevated-plus maze (EPM) and increased plasma corticosterone levels. Ethanol withdrawal significantly increased systolic blood pressure and plasma angiotensin II (ANG II) levels without an effect on plasma renin activity (PRA), angiotensin converting enzyme (ACE) activity, or plasma angiotensin I (ANG I) levels. No differences in vascular ANG I, ANG II levels, and ACE activity/expression and AT1 and AT2 receptor expression were detected among the experimental groups. Plasma osmolality, as well as plasma sodium, potassium, and glucose levels were not affected by ethanol withdrawal. Ethanol withdrawal induced systemic and vascular oxidative stress, as evidenced by increased plasma thiobarbituric acid-reacting substances (TBARS) levels and the vascular generation of superoxide anion. Ethanol withdrawal significantly decreased plasma and vascular nitrate/nitrite levels. Major new findings of the present study are that ethanol withdrawal induces vascular oxidative stress and reduces nitric oxide (NO) levels in the vasculature. Additionally, our study provides novel evidence that ethanol withdrawal does not affect the vascular ANG II generating system while stimulating systemic RAS. These responses could predispose individuals to the development of cardiovascular diseases.
authors.affiliation: Programa de pós-graduação em Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil; Escola de Enfermagem de Ribeirão Preto, Departamento de Enfermagem Psiquiátrica e Ciências Humanas, USP, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Gonzaga
authors.affiliation: Faculdade de Medicina de Ribeirão Preto, Departamento de Fisiologia, USP, Ribeirão Preto, São Paulo, Brazil.
authors.forename: André S
authors.initials: AS
authors.lastname: Mecawi
authors.affiliation: Faculdade de Medicina de Ribeirão Preto, Departamento de Fisiologia, USP, Ribeirão Preto, São Paulo, Brazil.
authors.forename: José
authors.initials: J
authors.lastname: Antunes-Rodrigues
authors.affiliation: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, USP, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Bruno S
authors.initials: BS
authors.lastname: De Martinis
authors.affiliation: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, USP, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Padovan
authors.affiliation: Escola de Enfermagem de Ribeirão Preto, Departamento de Enfermagem Psiquiátrica e Ciências Humanas, USP, Ribeirão Preto, São Paulo, Brazil. Electronic address: crtirapelli@eerp.usp.br.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Tirapelli
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001682:Biological Availability; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage* / Q000633:toxicity; D008297:Male; D009569:Nitric Oxide / Q000097:blood*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000097:blood* / Q000209:etiology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D017392:Thiobarbituric Acid Reactive Substances; D009569:Nitric Oxide; D000431:Ethanol
keywords: Ethanol withdrawal; Hypertension; NAD(P)H oxidase; Oxidative stress; Renin-angiotensin system; Superoxide anion