Acute ethanol intake induces superoxide anion generation and mitogen-activated protein kinase phosphorylation in rat aorta: A role for angiotensin type 1 receptor

Author(s)

Yogi, Alvaro ^[1] ; Callera, Glaucia E. ^[1] ; Mecawi, Andre S. ^[2] ; Batalhao, Marcelo E. ^[3] ; Carnio, Evelin C. ^[3] ; Antunes-Rodrigues, Jose ^[2] ; Queiroz, Regina H. ^[4] ; Touyz, Rhian M. ^[1] ; Tirapelli, Carlos R. ^[5]

Affiliation

^[1] Univ Ottawa, Ottawa Hosp, Res Inst, Kidney Res Ctr, Ottawa, ON K1N 6N5 - Canada

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Physiol, BR-14040902 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Coll Nursing Ribeirao Preto, Dept Gen & Specialized Nursing, BR-14040902 Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Clin Toxicol & Food Sci Anal, BR-14040902 Ribeirao Preto, SP - Brazil

^[5] Univ Sao Paulo, Escola Enfermagem Ribeirao Preto, Dept Psychiat Nursing & Human Sci, Lab Pharmacol, Coll Nursing Ribeirao Preto, BR-14040902 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Toxicology and Applied Pharmacology; v. 264, n. 3, p. 470-478, NOV 1 2012.
• Web of Science Citations: 31

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 ATI 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 AT(1)-dependent mechanisms. These findings highlight the importance of RAS in acute ethanol-induced oxidative damage. (c) 2012 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 10/05815-4 - Assessment of the role of angiotensin II in the cardiovascular effects induced by acute ethanol consumption
• Grantee: Carlos Renato Tirapelli
• Support Opportunities: Regular Research Grants