PMID- 29753230 OWN - NLM STAT- MEDLINE DCOM- 20191209 LR - 20191217 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 274 DP - 2018 Jul TI - Nebivolol prevents vascular oxidative stress and hypertension in rats chronically treated with ethanol. PG - 67-76 LID - S0021-9150(18)30226-0 [pii] LID - 10.1016/j.atherosclerosis.2018.04.041 [doi] AB - 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. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - do Vale, Gabriel T AU - do Vale GT AD - Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo (USP), Ribeirao Preto, SP, Brazil; Laboratory of Pharmacology, Department of Psychiatric Nursing and Human Sciences, School of Nursing of Ribeirao Preto, USP, Ribeirao Preto, Sao Paulo, Brazil. FAU - Simplicio, Janaina A AU - Simplicio JA AD - Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo (USP), Ribeirao Preto, SP, Brazil; Laboratory of Pharmacology, Department of Psychiatric Nursing and Human Sciences, School of Nursing of Ribeirao Preto, USP, Ribeirao Preto, Sao Paulo, Brazil. FAU - Gonzaga, Natalia A AU - Gonzaga NA AD - Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo (USP), Ribeirao Preto, SP, Brazil; Laboratory of Pharmacology, Department of Psychiatric Nursing and Human Sciences, School of Nursing of Ribeirao Preto, USP, Ribeirao Preto, Sao Paulo, Brazil. FAU - Yokota, Rodrigo AU - Yokota R AD - Department of Medicine, Division of Nephrology, Federal University of Sao Paulo, Sao Paulo, Brazil. FAU - Ribeiro, Amanda A AU - Ribeiro AA AD - Department of Medicine, Division of Nephrology, Federal University of Sao Paulo, Sao Paulo, Brazil. FAU - Casarini, Dulce E AU - Casarini DE AD - Department of Medicine, Division of Nephrology, Federal University of Sao Paulo, Sao Paulo, Brazil. FAU - de Martinis, Bruno S AU - de Martinis BS AD - Department of Chemistry, Faculty of Philosophy, Sciences and Letters of Ribeirao Preto, USP, Ribeirao Preto, Sao Paulo, Brazil. FAU - Tirapelli, Carlos R AU - Tirapelli CR AD - Laboratory of Pharmacology, Department of Psychiatric Nursing and Human Sciences, School of Nursing of Ribeirao Preto, USP, Ribeirao Preto, Sao Paulo, Brazil. Electronic address: crtirapelli@eerp.usp.br. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180430 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Adrenergic beta-1 Receptor Antagonists) RN - 0 (Antihypertensive Agents) RN - 0 (Biomarkers) RN - 030Y90569U (Nebivolol) RN - 31C4KY9ESH (Nitric Oxide) RN - 3604-79-3 (3-nitrotyrosine) RN - 3K9958V90M (Ethanol) RN - 42HK56048U (Tyrosine) RN - EC 1.11.1.6 (Catalase) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 1.6.3.- (NADPH Oxidases) RN - X4W3ENH1CV (Norepinephrine) RN - YKH834O4BH (Epinephrine) SB - IM MH - Adrenergic beta-1 Receptor Antagonists/*pharmacology MH - Animals MH - Antihypertensive Agents/*pharmacology MH - Aorta, Thoracic/*drug effects/innervation/metabolism MH - Arterial Pressure/*drug effects MH - Biomarkers/metabolism MH - Catalase/metabolism MH - Disease Models, Animal MH - Epinephrine/blood MH - *Ethanol MH - Hypertension/chemically induced/metabolism/physiopathology/*prevention & control MH - Lipid Peroxidation/drug effects MH - Male MH - NADPH Oxidases/metabolism MH - Nebivolol/*pharmacology MH - Nitric Oxide/metabolism MH - Norepinephrine/blood MH - Oxidative Stress/*drug effects MH - Rats, Wistar MH - Renin-Angiotensin System/drug effects MH - Superoxide Dismutase/metabolism MH - Sympathetic Nervous System/drug effects/metabolism/physiopathology MH - Tyrosine/analogs & derivatives/metabolism OTO - NOTNLM OT - Ethanol OT - Hypertension OT - Nebivolol OT - Oxidative stress OT - beta(1)-adrenergic receptors EDAT- 2018/05/13 06:00 MHDA- 2019/12/18 06:00 CRDT- 2018/05/13 06:00 PHST- 2018/02/05 00:00 [received] PHST- 2018/04/16 00:00 [revised] PHST- 2018/04/27 00:00 [accepted] PHST- 2018/05/13 06:00 [pubmed] PHST- 2019/12/18 06:00 [medline] PHST- 2018/05/13 06:00 [entrez] AID - S0021-9150(18)30226-0 [pii] AID - 10.1016/j.atherosclerosis.2018.04.041 [doi] PST - ppublish SO - Atherosclerosis. 2018 Jul;274:67-76. doi: 10.1016/j.atherosclerosis.2018.04.041. Epub 2018 Apr 30.