title: Angiotensin type 1 receptor mediates chronic ethanol consumption-induced hypertension and vascular oxidative stress.
abstract: OBJECTIVE
  We hypothesized that chronic ethanol intake enhances vascular oxidative stress and induces hypertension through renin-angiotensin system (RAS) activation.
  
  
  RESULTS
  Male Wistar rats were treated with ethanol (20% v/v). The increase in blood pressure induced by ethanol was prevented by losartan (10mg/kg/day; p.o. gavage), a selective AT1 receptor antagonist. Chronic ethanol intake increased plasma renin activity (PRA), angiotensin converting enzyme (ACE) activity, plasma angiotensin I (ANG I) and angiotensin II (ANG II) levels and serum aldosterone levels. No differences on plasma osmolality and sodium or potassium levels were detected after treatment with ethanol. Ethanol consumption did not alter ACE activity, as well as the levels of ANG I and ANG II in the rat aorta or mesenteric arterial bed (MAB). Ethanol induced systemic and vascular oxidative stress (aorta and MAB) and these effects were prevented by losartan. The decrease on plasma and vascular nitrate/nitrite (NOx) levels induced by ethanol was prevented by losartan. Ethanol intake did not alter protein expression of ACE, AT1 or AT2 receptors in both aorta and MAB. Aortas from ethanol-treated rats displayed decreased ERK1/2 phosphorylation and increased protein expression of SAPK/JNK. These responses were prevented by losartan. MAB from ethanol-treated rats displayed reduced phosphorylation of p38MAPK and ERK1/2 and losartan did not prevent these responses.
  
  
  CONCLUSIONS
  Our study provides novel evidence that chronic ethanol intake increases blood pressure, induces vascular oxidative stress and decreases nitric oxide (NO) bioavailability through AT1-dependent mechanisms.
authors: Programa de pós-graduação em Toxicologia, Faculdade de Ciências Farmacêuticas 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: Patrícia
authors: P
authors: Passaglia
authors: Escola de Enfermagem de Ribeirão Preto, Laboratório de Farmacologia, USP, Ribeirão Preto, São Paulo, Brazil.
authors: Carla S
authors: CS
authors: Ceron
authors: Faculdade de Medicina de Ribeirão Preto, USP, Ribeirão Preto, São Paulo, Brazil.
authors: André S
authors: AS
authors: Mecawi
authors: Faculdade de Medicina de Ribeirão Preto, USP, Ribeirão Preto, São Paulo, Brazil.
authors: José
authors: J
authors: Antunes-Rodrigues
authors: Faculdade de Medicina de Ribeirão Preto, USP, Ribeirão Preto, São Paulo, Brazil.
authors: Eduardo B
authors: EB
authors: Coelho
authors: Escola de Enfermagem de Ribeirão Preto, Laboratório de Farmacologia, USP, Ribeirão Preto, São Paulo, Brazil. Electronic address: crtirapelli@eerp.usp.br.
authors: Carlos R
authors: CR
authors: Tirapelli
mesh_terms: D000428:Alcohol Drinking / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000009:adverse effects* / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D000431:Ethanol; D019808:Losartan
keywords: Angiotensin II; Ethanol; Hypertension; Oxidative stress; Superoxide anion