Acute ethanol intake induces NAD(P)H oxidase activation and RhoA translocation in resistance arteries

Simplicio, J. A., Hipólito, U. V., Tavares do Vale, G., Callera, G. E., Pereira, C. A., Touyz, R. M. , de Cássia Tostes, R. and Tirapelli, C. R. (2016) Acute ethanol intake induces NAD(P)H oxidase activation and RhoA translocation in resistance arteries. Arquivos Brasileiros de Cardiologia, 107(5), pp. 427-436. (doi: 10.5935/abc.20160147) (PMID:27812679) (PMCID:PMC5137387)

[img]
Preview
Text
120005.pdf - Published Version
Available under License Creative Commons Attribution.

1MB

Abstract

Background: The mechanism underlying the vascular dysfunction induced by ethanol is not totally understood. Identification of biochemical/molecular mechanisms that could explain such effects is warranted. Objective: To investigate whether acute ethanol intake activates the vascular RhoA/Rho kinase pathway in resistance arteries and the role of NAD(P)H oxidase-derived reactive oxygen species (ROS) on such response. We also evaluated the requirement of p47phox translocation for ethanol-induced NAD(P)H oxidase activation. Methods: Male Wistar rats were orally treated with ethanol (1g/kg, p.o. gavage) or water (control). Some rats were treated with vitamin C (250 mg/kg, p.o. gavage, 5 days) before administration of water or ethanol. The mesenteric arterial bed (MAB) was collected 30 min after ethanol administration. Results: Vitamin C prevented ethanol-induced increase in superoxide anion (O2 - ) generation and lipoperoxidation in the MAB. Catalase and superoxide dismutase activities and the reduced glutathione, nitrate and hydrogen peroxide (H2 O2 ) levels were not affected by ethanol. Vitamin C and 4-methylpyrazole prevented the increase on O2 - generation induced by ethanol in cultured MAB vascular smooth muscle cells. Ethanol had no effect on phosphorylation levels of protein kinase B (Akt) and eNOS (Ser1177 or Thr495 residues) or MAB vascular reactivity. Vitamin C prevented ethanol-induced increase in the membrane: cytosol fraction ratio of p47phox and RhoA expression in the rat MAB. Conclusion: Acute ethanol intake induces activation of the RhoA/Rho kinase pathway by a mechanism that involves ROS generation. In resistance arteries, ethanol activates NAD(P)H oxidase by inducing p47phox translocation by a redox-sensitive mechanism. (Arq Bras Cardiol. 2016; 107(5):427-436)

Item Type:Articles
Additional Information:This study was funded by Fundação de Amparo à Pesquisa do Estado de São Paulo.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Touyz, Professor Rhian
Authors: Simplicio, J. A., Hipólito, U. V., Tavares do Vale, G., Callera, G. E., Pereira, C. A., Touyz, R. M., de Cássia Tostes, R., and Tirapelli, C. R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Arquivos Brasileiros de Cardiologia
Journal Abbr.:Arq Bras Cardiol
Publisher:Sociedade Brasileira de Cardiologia
ISSN:0066-782X
ISSN (Online):1678-4170
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Arquivos Brasileiros de Cardiologia 107(5): 427-436
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record