Reactive oxygen species derived from NAD(P)H oxidase play a role on ethanol-induced hypertension and endothelial dysfunction in rat resistance arteries

• Published in: Journal of physiology and biochemistry 2017-02, Vol.73 (1), p.5-16
• Main Authors: Simplicio, Janaina A., do Vale, Gabriel T., Gonzaga, Natália A., Leite, Letícia N., Hipólito, Ulisses V., Pereira, Camila A., Tostes, Rita C., Tirapelli, Carlos R.
• Format: Article
• Language: English
• Subjects: Acetophenones - therapeutic use; Acetylcholine; Alcoholism - physiopathology; Animal Physiology; Animals; Arteries; Biomedical and Life Sciences; Biomedicine; Blood pressure; Cardiovascular diseases; Cardiovascular Diseases - etiology; Cardiovascular Diseases - immunology; Cardiovascular Diseases - prevention & control; Catalase; CYBB protein; Cytokines - blood; Disease Models, Animal; Endothelium, Vascular - drug effects; Endothelium, Vascular - immunology; Endothelium, Vascular - metabolism; Endothelium, Vascular - physiopathology; Enzyme Inhibitors - therapeutic use; Ethanol; Gene Expression Regulation, Enzymologic - drug effects; Glutathione; Human Physiology; Hydrogen peroxide; Hypertension; Hypertension - etiology; Hypertension - metabolism; Hypertension - physiopathology; Hypertension - prevention & control; Interleukin 10; Interleukin 6; JNK protein; Male; MAP Kinase Signaling System - drug effects; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Mesenteric Arteries - drug effects; Mesenteric Arteries - immunology; Mesenteric Arteries - metabolism; Mesenteric Arteries - physiopathology; NAD; NAD(P)H oxidase; NADPH Oxidase 2; NADPH Oxidases - antagonists & inhibitors; NADPH Oxidases - genetics; NADPH Oxidases - metabolism; Nitrates; Nitric Oxide Synthase Type III - genetics; Nitric Oxide Synthase Type III - metabolism; Nitrites; NOX4 protein; Original Article; Oxidative Stress - drug effects; Phosphorylation; Phosphorylation - drug effects; Plasma levels; Random Allocation; Rats, Wistar; Reactive oxygen species; Reactive Oxygen Species - antagonists & inhibitors; Reactive Oxygen Species - metabolism; Superoxide dismutase; Tumor necrosis factor; Tumor necrosis factor-TNF; Vascular Resistance - drug effects; Veins & arteries
• ISSN: 1138-7548; 1877-8755
• DOI: 10.1007/s13105-016-0519-z

Chronic ethanol consumption is a risk factor for cardiovascular diseases. We studied whether NAD(P)H oxidase-derived reactive oxygen species (ROS) play a role in ethanol-induced hypertension, vascular dysfunction, and protein expression in resistance arteries. Male Wistar rats were treated with ethanol (20 %  v / v ) for 6 weeks. Ethanol treatment increased blood pressure and decreased acetylcholine-induced relaxation in the rat mesenteric arterial bed (MAB). These responses were attenuated by apocynin (30 mg/kg/day; p.o. gavage). Ethanol consumption increased superoxide anion (O 2 − ) generation and decreased nitrate/nitrite (NO x ) concentration in the rat MAB and apocynin prevented these responses. Conversely, ethanol did not affect the concentration of hydrogen peroxide (H 2 O 2 ) and reduced glutathione (GSH) or the activity of superoxide dismutase (SOD) and catalase (CAT) in the rat MAB. Ethanol increased interleukin (IL)-10 levels in the rat MAB but did not affect the levels of tumor necrosis factor (TNF)-α, IL-6, or IL-1β. Ethanol increased the expression of Nox2 and the phosphorylation of SAPK/JNK, but reduced eNOS expression in the rat MAB. Apocynin prevented these responses. However, ethanol treatment did not affect the expression of Nox1, Nox4, p38MAPK, ERK1/2, or SAPK/JNK in the rat MAB. Ethanol increased plasma levels of TBARS, TNF-α, IL-6, IL-1β, and IL-10, whereas it decreased NO x levels. The major finding of our study is that NAD(P)H oxidase-derived ROS play a role on ethanol-induced hypertension and endothelial dysfunction in resistance arteries. Moreover, ethanol consumption affects the expression and phosphorylation of proteins that regulate vascular function and NAD(P)H oxidase-derived ROS play a role in such responses.