Chronic ethanol consumption increases blood pressure and induces vascular dysfunction and oxidative stress through mineralocorticoid receptor activation

Chronic ethanol consumption increases blood pressure and induces vascular dysfunction and oxidative stress through mineralocorticoid receptor activation

• Autor
• Thales de Mileto Henrique Dourado
• Co-autores
• Wanessa Mayumi Carvalho Awata , Carlos Renato Tirapelli
• Resumo

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  Introduction: Chronic ethanol consumption increases blood pressure, vascular contractility and oxidative stress through activation of the renin-angiotensin-aldosterone system. Aldosterone acts on mineralocorticoid receptor (MR) to promote vascular inflammation and oxidative stress leading to vascular dysfunction. This study aimed to investigate whether aldosterone increases blood pressure and induces oxidative stress in the vasculature of rats chronically treated with ethanol. Methods: Male Wistar Hannover rats (250-300g) were distributed in 4 groups: Control: animals received water ad libitum for 5 weeks and daily gavage of vehicle (C) or an MR antagonist [potassium canrenoate, 30mg/kg/day, (CP)]; Ethanol: animals were treated with ethanol 20% (v/v) for 5 weeks and vehicle (E) or CP (E + CP). Blood and thoracic aorta were collected for biochemical analysis. Concentration-response curves for phenylephrine were obtained in aortic rings with (E+) or without (E-) endothelium, in the absence or after incubation (30min) with tiron (10 µmol/l, superoxide scavenger). Results were analyzed using two-way ANOVA. Results: Ethanol increased aldosterone serum levels (pg/ml) (C=612.8±11.5; CP=614.5±7.6; E=662.7±5.7*; E +CP=668.2±7.0*; n=6-8) and treatment with potassium canrenoato did not prevent this response. Ethanol also increased systolic (mmHg) (C=115.8±4.8; CP=117.4±5.0; E=144.5±2.5*; E+CP=124.3±5.1; n=5-7) and diastolic blood pressure (mmHg) (C=77.8±1.9; CP=83.3±3.1; E=99.8±2.4*; E+CP=87.6±1.5; n=5-7). Increased levels of O2- (RLU/mg protein) (C=6.9±0.7; CP=9.2±0.8; E=16.9±1.2*; E+CP=7.1±1.5; n=6) and TBARS (mol/mg protein) (C=1.0±0.1; CP=1.1±0.1; E=2.9±0.5*; E+CP=1.0±0.1; n=7-8) were found in the aorta of ethanol-treated rats. Treatment with CP prevented these responses. Ethanol increased maximal response to phenylephrine (mN) in E+ rings (C=10.8±0.4; CP=11.5±0.5; E=15.8±0.5*; E+CP=9.9±0.6; n=5-8) and E- rings (C=16.1±0.7; CP=15.1±0.2; E=21.1±0.9*; E+CP=15.3±1.3; n=5-8). Treatment with CP prevented these responses. Incubation of aortic rings with tiron reversed ethanol-induced hyper-reactivity of E+ (11.6±1.2; n=6) and E- rings (15.1±0.6; n=8). Conclusion:  MR modulates the increase in blood pressure and vascular hyper-contractility induced by ethanol, which is associated with reactive oxygen species generation.

   

   

   

• Palavras-chave
• Ethanol, Vascular dysfunction, Aldosterone, Oxidative stress
• Área Temática
• Apresentações Orais - Sessão IX

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