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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 AT{sub 1} 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 thatmore » acute ethanol intake stimulates RAS activity and induces vascular oxidative stress and redox-signaling activation through AT{sub 1}-dependent mechanisms. These findings highlight the importance of RAS in acute ethanol-induced oxidative damage. -- Highlights: ► Acute ethanol intake stimulates RAS activity and vascular oxidative stress. ► RAS plays a role in acute ethanol-induced oxidative damage via AT{sub 1} receptor activation. ► Translocation of p47phox and MAPKs phosphorylation are downstream effectors. ► Acute ethanol consumption increases the risk for acute vascular injury.« less

Authors:
;  [1];  [2]; ;  [3];  [2];  [4];  [1];  [5]
  1. Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario (Canada)
  2. Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP (Brazil)
  3. Department of General and Specialized Nursing, College of Nursing of Ribeirão Preto, USP, São Paulo (Brazil)
  4. Department of Clinical, Toxicological and Food Science Analysis, Faculty of Pharmaceutical Sciences, USP, São Paulo (Brazil)
  5. Department of Psychiatric Nursing and Human Sciences, Laboratory of Pharmacology, College of Nursing of Ribeirão Preto, USP, Ribeirão Preto, SP (Brazil)
Publication Date:
OSTI Identifier:
22215968
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 264; Journal Issue: 3; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACETYLCHOLINE; ANGIOTENSIN; ANIONS; AORTA; BLOOD PRESSURE; DAMAGE; ENDOTHELIUM; ETHANOL; INJURIES; INTAKE; NAD; NITRATES; NITRIC OXIDE; OXIDATION; PHOSPHORYLATION; PHOSPHOTRANSFERASES; PLASMA; RATS; RECEPTORS; RENIN; TRANSLOCATION

Citation Formats

Yogi, Alvaro, Callera, Glaucia E., Mecawi, André S., Batalhão, Marcelo E., Carnio, Evelin C., Antunes-Rodrigues, José, Queiroz, Regina H., Touyz, Rhian M., and Tirapelli, Carlos R., E-mail: crtirapelli@eerp.usp.br. Acute ethanol intake induces superoxide anion generation and mitogen-activated protein kinase phosphorylation in rat aorta: A role for angiotensin type 1 receptor. United States: N. p., 2012. Web. doi:10.1016/J.TAAP.2012.08.029.
Yogi, Alvaro, Callera, Glaucia E., Mecawi, André S., Batalhão, Marcelo E., Carnio, Evelin C., Antunes-Rodrigues, José, Queiroz, Regina H., Touyz, Rhian M., & Tirapelli, Carlos R., E-mail: crtirapelli@eerp.usp.br. Acute ethanol intake induces superoxide anion generation and mitogen-activated protein kinase phosphorylation in rat aorta: A role for angiotensin type 1 receptor. United States. doi:10.1016/J.TAAP.2012.08.029.
Yogi, Alvaro, Callera, Glaucia E., Mecawi, André S., Batalhão, Marcelo E., Carnio, Evelin C., Antunes-Rodrigues, José, Queiroz, Regina H., Touyz, Rhian M., and Tirapelli, Carlos R., E-mail: crtirapelli@eerp.usp.br. Thu . "Acute ethanol intake induces superoxide anion generation and mitogen-activated protein kinase phosphorylation in rat aorta: A role for angiotensin type 1 receptor". United States. doi:10.1016/J.TAAP.2012.08.029.
@article{osti_22215968,
title = {Acute ethanol intake induces superoxide anion generation and mitogen-activated protein kinase phosphorylation in rat aorta: A role for angiotensin type 1 receptor},
author = {Yogi, Alvaro and Callera, Glaucia E. and Mecawi, André S. and Batalhão, Marcelo E. and Carnio, Evelin C. and Antunes-Rodrigues, José and Queiroz, Regina H. and Touyz, Rhian M. and Tirapelli, Carlos R., E-mail: crtirapelli@eerp.usp.br},
abstractNote = {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 AT{sub 1} 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{sub 1}-dependent mechanisms. These findings highlight the importance of RAS in acute ethanol-induced oxidative damage. -- Highlights: ► Acute ethanol intake stimulates RAS activity and vascular oxidative stress. ► RAS plays a role in acute ethanol-induced oxidative damage via AT{sub 1} receptor activation. ► Translocation of p47phox and MAPKs phosphorylation are downstream effectors. ► Acute ethanol consumption increases the risk for acute vascular injury.},
doi = {10.1016/J.TAAP.2012.08.029},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 3,
volume = 264,
place = {United States},
year = {2012},
month = {11}
}