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Reactive oxygen species derived from NAD(P)H oxidase play a role on ethanol-induced hypertension and endothelial dysfunction in rat resistance arteries

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Abstract

Chronic ethanol consumption is a risk factor for cardiovascular diseases. We studied whether NAD(P)H oxidase-derived reactive oxygen species (ROS) play a role in ethanol-induced hypertension, vascular dysfunction, and protein expression in resistance arteries. Male Wistar rats were treated with ethanol (20 % v/v) for 6 weeks. Ethanol treatment increased blood pressure and decreased acetylcholine-induced relaxation in the rat mesenteric arterial bed (MAB). These responses were attenuated by apocynin (30 mg/kg/day; p.o. gavage). Ethanol consumption increased superoxide anion (O2 −) generation and decreased nitrate/nitrite (NO x ) concentration in the rat MAB and apocynin prevented these responses. Conversely, ethanol did not affect the concentration of hydrogen peroxide (H2O2) and reduced glutathione (GSH) or the activity of superoxide dismutase (SOD) and catalase (CAT) in the rat MAB. Ethanol increased interleukin (IL)-10 levels in the rat MAB but did not affect the levels of tumor necrosis factor (TNF)-α, IL-6, or IL-1β. Ethanol increased the expression of Nox2 and the phosphorylation of SAPK/JNK, but reduced eNOS expression in the rat MAB. Apocynin prevented these responses. However, ethanol treatment did not affect the expression of Nox1, Nox4, p38MAPK, ERK1/2, or SAPK/JNK in the rat MAB. Ethanol increased plasma levels of TBARS, TNF-α, IL-6, IL-1β, and IL-10, whereas it decreased NO x levels. The major finding of our study is that NAD(P)H oxidase-derived ROS play a role on ethanol-induced hypertension and endothelial dysfunction in resistance arteries. Moreover, ethanol consumption affects the expression and phosphorylation of proteins that regulate vascular function and NAD(P)H oxidase-derived ROS play a role in such responses.

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Acknowledgments

This work was supported by grants from FAPESP [grant numbers 2013/03965-7 and 2013/15824-9].

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Authors and Affiliations

  1. Programa de pós-graduação em Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil

    Janaina A. Simplicio, Gabriel T. do Vale, Natália A. Gonzaga, Letícia N. Leite, Camila A. Pereira & Rita C. Tostes

  2. Laboratório de Farmacologia, DEPCH, Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, CEP 14040-902, Ribeirão Preto, SP, Brazil

    Janaina A. Simplicio, Gabriel T. do Vale, Natália A. Gonzaga, Letícia N. Leite, Ulisses V. Hipólito & Carlos R. Tirapelli

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  1. Janaina A. Simplicio
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Correspondence to Carlos R. Tirapelli.

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Simplicio, J.A., do Vale, G.T., Gonzaga, N.A. et al. Reactive oxygen species derived from NAD(P)H oxidase play a role on ethanol-induced hypertension and endothelial dysfunction in rat resistance arteries. J Physiol Biochem 73, 5–16 (2017). https://doi.org/10.1007/s13105-016-0519-z

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