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)

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 > School of Cardiovascular & Metabolic Health
• 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