Role of NADPH oxidase in increased blood pressure induced by chronic ethanol consumption: evaluation of vascular oxidative stress

Author(s)

Katia Colombo Marchi

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2015-11-30

Examining board members

Carlos Renato Tirapelli; Fernando Silva Carneiro; Jose Eduardo Tanus dos Santos

• Advisor: Carlos Renato Tirapelli

Abstract

Chronic ethanol consumption results in significant alterations in cardiac and circulatory functions, appearing as an important risk factor responsible for cardiovascular diseases such as hypertension. The initial step for cardiovascular dysfunction associated with ethanol consumption involves the generation of reactive oxygen species (ROS) and reduced bioavailability of nitric oxide (NO), processes mediated by the enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Based on the mentioned observations we hypothesized that ethanol consumption increases blood pressure, ROS generation and induces activation of redox-sensitive signaling pathways in the vasculature through NADPH oxidase. Thus, here we investigated the contribution of NADPH oxidase in chronic ethanol consumption-induced hypertension and vascular oxidative stress through its inhibition by apocynin. This study demonstrated for the first time the involvement of oxidative stress via ROS derived from NADPH oxidase in increased blood pressure induced by chronic ethanol intake. The increased contractility of endothelium-intact and endothelium-denuded aortic rings from ethanol-treated rats to phenylephrine was prevented by apocynin. Ethanol consumption increased systemic and vascular oxidative stress and apocynin prevented these responses. The decrease on plasma and vascular nitrate/nitrite (NOx) levels induced by ethanol were not prevented by apocynin. Treatment with ethanol did not affect aortic levels of hydrogen peroxide (H2O2) and reduced glutathione (GSH) as well as the activity of xanthine oxidase (XO), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Ethanol-induced increased protein expression of Nox1, PKC?, nNOS, SAPK/JNK and SOD2 in the rat aorta was prevented by apocynin. No difference on the 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, ERK1/2, c-Src, Rac1 or PKC?. The major new finding of our study is that the increased vascular generation of reactive oxygen species (ROS) induced by ethanol is related to the increased vascular Nox1/NADPH oxidase expression. This mechanism is involved on the 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 (AU)

• FAPESP's process: 12/01147-2 - Role of NAD(P)H oxidase in the cardiovascular effects induced by chronic ethanol consumption.
• Grantee: Katia Colombo Marchi
• Support Opportunities: Scholarships in Brazil - Doctorate