Angiotensin type 1 receptor mediates chronic ethanol consumption-induced hypertension and vascular oxidative stress

Author(s)

Passaglia, Patricia ^{[1, 2]} ; Ceron, Carla S. ^[1] ; Mecawi, Andre S. ^[3] ; Antunes-Rodrigues, Jose ^[3] ; Coelho, Eduardo B. ^[3] ; Tirapelli, Carlos R. ^[1]

Affiliation

^[1] Univ Sao Paulo, Escola Enfermagem Ribeirao Preto, Farmacol Lab, BR-14040902 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Programa Posgrad Toxicol, BR-14040902 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Fac Med Ribeirao Preto, BR-14040902 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: VASCULAR PHARMACOLOGY; v. 74, p. 49-59, NOV 2015.
• Web of Science Citations: 23

Abstract

Objectives: We hypothesized that chronic ethanol intake enhances vascular oxidative stress and induces hypertension through renin-angiotensin system (RAS) activation. Methods and results: Male Wistar rats were treated with ethanol (20% v/v). The increase in blood pressure induced by ethanol was prevented by losartan (10 mg/kg/day; p.o. gavage), a selective AT(1) 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, AT(1) or AT(2) 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 AT(1)-dependent mechanisms. (C) 2015 Elsevier Inc All rights reserved. (AU)

• FAPESP's process: 12/10096-2 - Study of participation of Angiotensin II in cardiovascular dysfunction induced by chronic ethanol consumption
• Grantee: Patrícia Passaglia
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 10/05815-4 - Assessment of the role of angiotensin II in the cardiovascular effects induced by acute ethanol consumption
• Grantee: Carlos Renato Tirapelli
• Support Opportunities: Regular Research Grants