Ulisses V Hipólito1, Glaucia E Callera2, Janaina A Simplicio1, Bruno S De Martinis3, Rhian M Touyz2, Carlos R Tirapelli4. 1. Programa de Pós-Graduação em Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil; Departamento de Enfermagem Psiquiátrica e Ciências Humanas, Laboratório de Farmacologia, Escola de Enfermagem de Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil. 2. Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada. 3. Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, USP, Ribeirão Preto, São Paulo, Brazil. 4. Departamento de Enfermagem Psiquiátrica e Ciências Humanas, Laboratório de Farmacologia, Escola de Enfermagem de Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil. Electronic address: crtirapelli@eerp.usp.br.
Abstract
AIMS: Investigate the effect of ascorbic acid (vitamin C) on the endothelial dysfunction induced by acute ethanol intake. MAIN METHODS: Ethanol (1g/kg; p.o. gavage) effects were assessed within 30min in male Wistar rats. KEY FINDINGS: Ethanol intake decreased the endothelium-dependent relaxation induced by acetylcholine in the rat aorta and treatment with vitamin C (250mg/kg; p.o. gavage, 5days) prevented this response. Ethanol increased superoxide anion (O2(-)) generation and decreased aortic nitrate/nitrite levels and these responses were not prevented by vitamin C. Superoxide dismutase (SOD) and catalase (CAT) activities as well as hydrogen peroxide (H2O2) and reduced glutathione (GSH) levels were not affected by ethanol. RhoA translocation as well as the phosphorylation levels of protein kinase B (Akt), eNOS (Ser(1177) or Thr(495) residues), p38MAPK, SAPK/JNK and ERK1/2 was not affected by ethanol intake. Vitamin C increased SOD activity and phosphorylation of Akt, eNOS (Ser(1177) residue) and p38MAPK in aortas from both control and ethanol-treated rats. Incubation of aortas with tempol prevented ethanol-induced decrease in the relaxation induced by acetylcholine. Ethanol (50mM/1min) increased O2(-) generation in cultured aortic vascular smooth muscle cells (VSMC) and vitamin C did not prevent this response. In endothelial cells, vitamin C prevented the increase on ROS generation and the decrease in the cytosolic NO content induced by ethanol. SIGNIFICANCE: Our study provides novel evidence that vitamin C prevents the endothelial dysfunction induced by acute ethanol intake by a mechanism that involves reduced ROS generation and increased NO availability in endothelial cells.
AIMS: Investigate the effect of ascorbic acid (vitamin C) on the endothelial dysfunction induced by acute ethanol intake. MAIN METHODS:Ethanol (1g/kg; p.o. gavage) effects were assessed within 30min in male Wistar rats. KEY FINDINGS:Ethanol intake decreased the endothelium-dependent relaxation induced by acetylcholine in the rat aorta and treatment with vitamin C (250mg/kg; p.o. gavage, 5days) prevented this response. Ethanol increased superoxide anion (O2(-)) generation and decreased aortic nitrate/nitrite levels and these responses were not prevented by vitamin C. Superoxide dismutase (SOD) and catalase (CAT) activities as well as hydrogen peroxide (H2O2) and reduced glutathione (GSH) levels were not affected by ethanol. RhoA translocation as well as the phosphorylation levels of protein kinase B (Akt), eNOS (Ser(1177) or Thr(495) residues), p38MAPK, SAPK/JNK and ERK1/2 was not affected by ethanol intake. Vitamin C increased SOD activity and phosphorylation of Akt, eNOS (Ser(1177) residue) and p38MAPK in aortas from both control and ethanol-treated rats. Incubation of aortas with tempol prevented ethanol-induced decrease in the relaxation induced by acetylcholine. Ethanol (50mM/1min) increased O2(-) generation in cultured aortic vascular smooth muscle cells (VSMC) and vitamin C did not prevent this response. In endothelial cells, vitamin C prevented the increase on ROS generation and the decrease in the cytosolic NO content induced by ethanol. SIGNIFICANCE: Our study provides novel evidence that vitamin C prevents the endothelial dysfunction induced by acute ethanol intake by a mechanism that involves reduced ROS generation and increased NO availability in endothelial cells.
Authors: Janaina A Simplicio; Ulisses Vilela Hipólito; Gabriel Tavares do Vale; Glaucia Elena Callera; Camila André Pereira; Rhian M Touyz; Rita de Cássia Tostes; Carlos R Tirapelli Journal: Arq Bras Cardiol Date: 2016-10-27 Impact factor: 2.000