Ethanol Withdrawal Alters the Oxidative State of the Heart Through AT(1)-Dependent Mechanisms

Author(s)

Assis, Victor O. ^[1] ; Gonzaga, Natalia A. ^{[2, 1]} ; Silva, Carla B. P. ^{[1, 3]} ; Pereira, Lucas C. ^[1] ; Padovan, Claudia M. ^[4] ; Tirapelli, Carlos R. ^[1]

Affiliation

^[1] Univ Sao Paulo, Escola Enfermagem Ribeirao Preto, Lab Farmacol, Ave Bandeirantes 3900, BR-14040902 Ribeirao Preto, SP - Brazil

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

^[3] Univ Sao Paulo, Programa Posgrad Toxicol, Fac Ciencias Farmaceut Ribeirao Preto, Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Dept Psicol, Fac Filosofia Ciencias & Letras Ribeirao Preto, Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: ALCOHOL AND ALCOHOLISM; v. 55, n. 1, p. 3-10, JAN 2020.
• Web of Science Citations: 0

Abstract

Aims: We investigated the cardiac effects of ethanol withdrawal and the possible role of AT(1) receptors in such response. Methods: Male Wistar rats were treated with increasing doses of ethanol (3 to 9%, vol./vol.) for 21 days. The cardiac effects of ethanol withdrawal were investigated 48 h after abrupt discontinuation of ethanol. Some animals were orally treated with losartan (10 mg/kg/day), a selective AT(1) receptor antagonist. Results: Ethanol withdrawal did not affect serum levels of creatine kinase (CK)-MB. Losartan prevented ethanol withdrawal-induced increase in superoxide anion (O-2 center dot(-)) production in the left ventricle (LV). However, ethanol withdrawal did no alter the levels of thiobarbituric acid reactive substances (TBARS) or the expression of Nox1, Nox2 or Nox4 were found in the LV. Ethanol withdrawal reduced the concentration of hydrogen peroxide (H2O2) in the LV and this response was prevented by losartan. Ethanol withdrawal increased catalase activity in the LV and losartan attenuated this response. No changes on superoxide dismutase (SOD) activity or expression were detected in the LV during ethanol withdrawal. The expression of AT(1), AT(2) or angiotensin converting enzyme (ACE) was not affected by ethanol withdrawal. Similarly, no changes on the expression of ERK1/2, SAPK/JNK, COX-1 or COX-2 were found in the LV during ethanol withdrawal. Conclusions: Ethanol withdrawal altered the cardiac oxidative state through AT(1)-dependent mechanisms. Our findings showed a role for angiotensin II/AT(1) receptors in the initial steps of the cardiac effects induced by ethanol withdrawal. (AU)

• FAPESP's process: 15/22046-8 - Role of AT1 receptors on ethanol withdrawal-induced hypertension and vascular oxidative stress
• Grantee: Carlos Renato Tirapelli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/00808-8 - Consequences of ethanol withdrawal on the vasculature and the systemic and local renin-angiotensin system (ras)
• Grantee: Carlos Renato Tirapelli
• Support Opportunities: Regular Research Grants