title: Reactive oxygen species derived from NAD(P)H oxidase play a role on ethanol-induced hypertension and endothelial dysfunction in rat resistance arteries.
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 (NOx) 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 NOxlevels. 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.
authors.affiliation: Programa de pós-graduação em Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.|Laboratório de Farmacologia, DEPCH, Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, CEP 14040-902, Ribeirão Preto, SP, Brazil.
authors.forename: Janaina A
authors.initials: JA
authors.lastname: Simplicio
authors.affiliation: Programa de pós-graduação em Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.|Laboratório de Farmacologia, DEPCH, Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, CEP 14040-902, Ribeirão Preto, SP, Brazil.
authors.forename: Gabriel T
authors.initials: GT
authors.lastname: do Vale
authors.affiliation: Programa de pós-graduação em Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.|Laboratório de Farmacologia, DEPCH, Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, CEP 14040-902, Ribeirão Preto, SP, Brazil.
authors.forename: Natália A
authors.initials: NA
authors.lastname: Gonzaga
authors.affiliation: Programa de pós-graduação em Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.|Laboratório de Farmacologia, DEPCH, Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, CEP 14040-902, Ribeirão Preto, SP, Brazil.
authors.forename: Letícia N
authors.initials: LN
authors.lastname: Leite
authors.affiliation: Laboratório de Farmacologia, DEPCH, Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, CEP 14040-902, Ribeirão Preto, SP, Brazil.
authors.forename: Ulisses V
authors.initials: UV
authors.lastname: Hipólito
authors.affiliation: Programa de pós-graduação em Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.
authors.forename: Camila A
authors.initials: CA
authors.lastname: Pereira
authors.affiliation: Programa de pós-graduação em Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.
authors.forename: Rita C
authors.initials: RC
authors.lastname: Tostes
authors.affiliation: Laboratório de Farmacologia, DEPCH, Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, CEP 14040-902, Ribeirão Preto, SP, Brazil. crtirapelli@eerp.usp.br.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Tirapelli
mesh_terms: D000098:Acetophenones / Q000627:therapeutic use; D000437:Alcoholism / Q000503:physiopathology; D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006973:Hypertension / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008638:Mesenteric Arteries / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011897:Random Allocation; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000098:Acetophenones; D016207:Cytokines; D004791:Enzyme Inhibitors; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; C056165:acetovanillone; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases
keywords: Apocynin; Ethanol; Hypertension; Oxidative stress; Superoxide anion