title: Acute ethanol intake induces superoxide anion generation and mitogen-activated protein kinase phosphorylation in rat aorta: a role for angiotensin type 1 receptor.
abstract: Ethanol intake is associated with increase in blood pressure, through unknown mechanisms. We hypothesized that acute ethanol intake enhances vascular oxidative stress and induces vascular dysfunction through renin-angiotensin system (RAS) activation. Ethanol (1 g/kg; p.o. gavage) effects were assessed within 30 min in male Wistar rats. The transient decrease in blood pressure induced by ethanol was not affected by the previous administration of losartan (10 mg/kg; p.o. gavage), a selective AT₁ receptor antagonist. Acute ethanol intake increased plasma renin activity (PRA), angiotensin converting enzyme (ACE) activity, plasma angiotensin I (ANG I) and angiotensin II (ANG II) levels. Ethanol induced systemic and vascular oxidative stress, evidenced by increased plasma thiobarbituric acid-reacting substances (TBARS) levels, NAD(P)H oxidase-mediated vascular generation of superoxide anion and p47phox translocation (cytosol to membrane). These effects were prevented by losartan. Isolated aortas from ethanol-treated rats displayed increased p38MAPK and SAPK/JNK phosphorylation. Losartan inhibited ethanol-induced increase in the phosphorylation of these kinases. Ethanol intake decreased acetylcholine-induced relaxation and increased phenylephrine-induced contraction in endothelium-intact aortas. Ethanol significantly decreased plasma and aortic nitrate levels. These changes in vascular reactivity and in the end product of endogenous nitric oxide metabolism were not affected by losartan. Our study provides novel evidence that acute ethanol intake stimulates RAS activity and induces vascular oxidative stress and redox-signaling activation through AT₁-dependent mechanisms. These findings highlight the importance of RAS in acute ethanol-induced oxidative damage.
authors.affiliation: Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario, Canada.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Yogi
authors.forename: Glaucia E
authors.initials: GE
authors.lastname: Callera
authors.forename: André S
authors.initials: AS
authors.lastname: Mecawi
authors.forename: Marcelo E
authors.initials: ME
authors.lastname: Batalhão
authors.forename: Evelin C
authors.initials: EC
authors.lastname: Carnio
authors.forename: José
authors.initials: J
authors.lastname: Antunes-Rodrigues
authors.forename: Regina H
authors.initials: RH
authors.lastname: Queiroz
authors.forename: Rhian M
authors.initials: RM
authors.lastname: Touyz
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Tirapelli
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage* / Q000097:blood / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism; D009566:Nitrates; D018384:Oxidative Stress; D010766:Phosphorylation / Q000187:drug effects; D021122:Protein Subunits; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013481:Superoxides / Q000378:metabolism*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D009566:Nitrates; D021122:Protein Subunits; D044140:Receptor, Angiotensin, Type 1; D013481:Superoxides; D000431:Ethanol; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D020929:Mitogen-Activated Protein Kinase Kinases; D019808:Losartan