Vascular Oxidative Stress: A Key Factor in the Development of Hypertension Associated with Ethanol Consumption

Abstract

The observation that the excessive consumption of ethyl alcohol (ethanol) is associated with high blood pressure is nearing its centennial mark. Mechanisms linking ethanol consumption and hypertension are complex and not fully understood. It is established that chronic ethanol consumption leads to hypertension and that this process is a multimediated event involving increased sympathetic activity, stimulation of the renin-angiotensin-aldosterone system with a subsequent increase in vascular oxidative stress and endothelial dysfunction. Under physiological conditions, reactive oxygen species (ROS) play an important role as a signaling molecule in the control of vascular tone and endothelial function. Increased ROS bioavailability is associated with important processes underlying vascular injury in cardiovascular disease such as endothelial dysfunction, vascular remodeling, and inflammation. Studies focusing on molecular mechanisms showed a link between overproduction of ROS in the vasculature and ethanol-induced hypertension. Of the ROS generated in vascular cells, superoxide anion (O2(-)) and hydrogen peroxide (H2O2) appear to be especially important. Ethanol-mediated generation of O2(-) and H2O2 in vascular tissues is associated with elevations in intracellular calcium ([Ca(2+)]i), reduced nitric oxide (NO) bioavailability, endothelial dysfunction and vasoconstriction. O2(-) can also act as a vascular signaling molecule regulating signaling pathways that lead to vascular contraction. Thus, through increased generation of ROS and activation of redox-sensitive pathways, ethanol induces vascular dysfunction, a response that might contribute to the hypertension associated with ethanol consumption. The present article reviews the role of ROS in vascular (patho)biology of ethanol.

Effects of Alcohol on the Cardiovascular System in Women

“…Various studies with animals and humans indicate that ethanol can increase the development of reactive oxygen species (ROS), leading to increases in redox-signaling pathways and decreases in protective antioxidant levels. Alcohol also can increase levels of co-enzymes or reducing equivalents (e.g., reduced nicotinamide adenine dinucleotide phosphate [NADPH]), which lead to increases in ROS formation and decreases in eNOS activity ( Ceron et al 2014 ). Several excellent reviews offer more detailed assessments of vascular cellular mechanisms ( Cahill and Redmond 2012 ; Husain et al 2014 ; Marchi et al 2014 ; Toda and Ayajiki 2010 ).…”

Development of an Adverse Outcome Pathway for the Onset of Hypertension by Oxidative Stress-Mediated Perturbation of Endothelial Nitric Oxide Bioavailability

“…Given the sealed nature of the circulatory system and high reactivity of oxidative radicals, vascular oxidative stress tends to arise from secondary generation of oxidant species following the action of xenobiotics and/or dietary and lifestyle factors, as opposed to exposure to direct acting oxidants, which are more likely to react with more proximal tissues related to the route of exposure. [18][19][20] Known secondary oxidant species include superoxide, peroxynitrite, hydroxyl radicals, lipid/protein peroxides, and carbonyls. 21 In vitro studies in endothelial cells have shown that exposure to chemicals, such as hydrogen peroxide, tertbutyl hydroperoxide, glucose, ultrafine particles (UFPs) derived from ambient air, 4-hydroxynonenal (4-HNE), and methylglyoxal, lowers the intracellular GSH content of human umbilical vein and pulmonary aortic endothelial cells.…”

Acute Ethanol Intake Induces NAD(P)H Oxidase Activation and Rhoa Translocation in Resistance Arteries

“…7,8 The enzyme nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase is the main source of ROS in endothelial and vascular smooth muscle cells (VSMC), 9 and a an essential factor in ethanol-induced vascular dysfunction. 10 The activation of NAD(P)H oxidase is a complex process , but translocation of the cytosolic subunit p47phox to the membrane, with further association with the cytochrome b 558 , is a decisive step for the activation of the enzyme . 11 Recent findings from our laboratory have shown that acute ethanol intake increases the generation of NAD(P)H oxidase-derived ROS in resistance arteries.…”