title: NADPH Oxidase Plays a Role on Ethanol-Induced Hypertension and Reactive Oxygen Species Generation in the Vasculature.
abstract: OBJECTIVE
  Investigate the role of NADPH oxidase on ethanol-induced hypertension and vascular oxidative stress.
  
  
  METHODS
  Male Wistar rats were treated with ethanol (20% v/v).
  
  
  RESULTS
  Apocynin (10 mg/kg/day, i.p.) prevented ethanol-induced hypertension. The increased contractility of endothelium-intact and endothelium-denuded aortic rings from ethanol-treated rats to phenylephrine was prevented by apocynin. Ethanol consumption increased superoxide anion (O2 (-)) generation and lipid peroxidation and apocynin prevented these responses. The decrease on plasma and vascular nitrate/nitrite (NOx) levels induced by ethanol was not prevented by apocynin. Treatment with ethanol did not affect aortic levels of hydrogen peroxide (H2O2) or reduced glutathione (GSH). Ethanol did not alter the activities of xanthine oxidase (XO), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Ethanol increased the expression of Nox1, PKCδ, nNOS, SAPK/JNK and SOD2 in the rat aorta and apocynin prevented these responses. No difference on aortic expression of Nox2, Nox4, p47phox, Nox organizer 1 (Noxo1), eNOS and iNOS was detected after treatment with ethanol. Ethanol treatment did not alter the phosphorylation of SAPK/JNK, p38MAPK, c-Src, Rac1 or PKCδ.
  
  
  CONCLUSIONS
  The major new finding of our study is that the increased vascular generation of reactive oxygen species (ROS) induced by ethanol is related to increased vascular Nox1/NADPH oxidase expression. This mechanism is involved in vascular dysfunction and hypertension induced by ethanol. Additionally, we conclude that ethanol consumption induces the expression of different proteins that regulate vascular contraction and growth and that NADPH oxidase-derived ROS play a role in such response.
  
  
  OBJECTIVE
  The key findings of our study are that ethanol-induced hypertension is mediated by NADPH oxidase. Moreover, increased vascular Nox1 expression is related to the generation of reactive oxygen species (ROS) by ethanol. Finally, ROS induced by ethanol increase the expression of the regulatory vascular proteins.
authors.affiliation: Departamento de Farmacologia da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil Escola de Enfermagem de Ribeirão Preto, Laboratório de Farmacologia, USP, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Katia Colombo
authors.initials: KC
authors.lastname: Marchi
authors.affiliation: Escola de Enfermagem de Ribeirão Preto, Laboratório de Farmacologia, USP, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Carla Speroni
authors.initials: CS
authors.lastname: Ceron
authors.affiliation: Escola de Enfermagem de Ribeirão Preto, Laboratório de Farmacologia, USP, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Jaqueline J
authors.initials: JJ
authors.lastname: Muniz
authors.affiliation: Faculdade de Filosofia Ciências e Letras de Ribeirão Preto, USP, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Bruno S
authors.initials: BS
authors.lastname: De Martinis
authors.affiliation: Departamento de Farmacologia da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.
authors.forename: José E
authors.initials: JE
authors.lastname: Tanus-Santos
authors.affiliation: Escola de Enfermagem de Ribeirão Preto, Laboratório de Farmacologia, USP, Ribeirão Preto, São Paulo, Brazil crtirapelli@eerp.usp.br.
authors.forename: Carlos Renato
authors.initials: CR
authors.lastname: Tirapelli
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000431:Ethanol / Q000009:adverse effects*; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000098:Acetophenones; D017382:Reactive Oxygen Species; D010656:Phenylephrine; D000431:Ethanol; C056165:acetovanillone; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases; D005978:Glutathione