Nebivolol prevents vascular oxidative stress and hypertension in rats chronically treated with ethanol

Author(s)

do Vale, Gabriel T. ^{[1, 2]} ; Simplicio, Janaina A. ^{[1, 2]} ; Gonzaga, Natalia A. ^{[1, 2]} ; Yokota, Rodrigo ^[3] ; Ribeiro, Amanda A. ^[3] ; Casarini, Dulce E. ^[3] ; de Martinis, Bruno S. ^[4] ; Tirapelli, Carlos R. ^[2]

Affiliation

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Pharmacol, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Sch Nursing Ribeirao Preto, Lab Pharmacol, Dept Psychiat Nursing & Human Sci, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Div Nephrol, Dept Med, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Dept Chem, Fac Philosophy Sci & Letters Ribeirao Preto, Sao Paulo - Brazil

• Document type: Journal article
• Source: ATHEROSCLEROSIS; v. 274, p. 67-76, JUL 2018.
• Web of Science Citations: 3

Abstract

Background and aims: Chronic ethanol consumption is associated with hypertension and atherosclerosis. Vascular oxidative stress is described as an important mechanism whereby ethanol predisposes to atherosclerosis. We hypothesized that nebivolol would prevent ethanol-induced hypertension and vascular oxidative stress. Methods: Male Wistar rats were treated with ethanol 20% (vol./vol.) or nebivolol (10 mg/kg/day, p. o., gavage), a selective beta(1)-adrenergic receptor antagonist. Results: Ethanol-induced increase in blood pressure and in the circulating levels of adrenaline and noradrenaline was prevented by nebivolol. Similarly, nebivolol prevented ethanol-induced increase in plasma levels of renin, angiotensin I and II. Chronic ethanol consumption increased the aortic levels of superoxide anion (O-2(-)), thiobarbituric acid reactive species (TBARS) as well as the expression of Nox1 and nitrotyrosine immunostaining in the rat aorta. Treatment with nebivolol prevented these responses. The decrease in aortic levels of nitrate/nitrite (NOx) induced by ethanol was prevented by the treatment with nebivolol. Finally, nebivolol attenuated ethanol-induced increase in phenylephrine- and noradrenaline-induced contraction of endothelium-intact and endothelium-denuded aortic rings. Conclusions: The novelty of our study is that nebivolol prevented ethanol-induced hypertension and vascular oxidative stress. Additionally, we showed that the sympathetic nervous system (SNS) and the renin-angiotensin system (RAS) are important endogenous mediators of the cardiovascular effects of ethanol. (C) 2018 Elsevier B.V. All rights reserved. (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