title: Arsenic, reactive oxygen, and endothelial dysfunction.
abstract: Human exposure to drinking water contaminated with arsenic is a serious global health concern and predisposes to cardiovascular disease states, such as hypertension, atherosclerosis, and microvascular disease. The most sensitive target of arsenic toxicity in the vasculature is the endothelium, and incubation of these cells with low concentrations of arsenite, a naturally occurring and highly toxic inorganic form of arsenic, rapidly induces reactive oxygen species (ROS) formation via activation of a specific NADPH oxidase (Nox2). Arsenite also induces ROS accumulation in vascular smooth muscle cells, but this is relatively delayed because, depending on the vessel from which they originate, these cells often lack Nox2 and/or its essential regulatory cytosolic subunits. The net effect of such activity is attenuation of endothelium-dependent conduit artery dilation via superoxide anion-mediated scavenging of nitric oxide (NO) and inhibition and downregulation of endothelial NO synthase, events that are temporally matched to the accumulation of oxidants across the vessel wall. By contrast, ROS induced by the more toxic organic trivalent arsenic metabolites (monomethylarsonous and dimethylarsinous acids) may originate from sources other than Nox2. As such, the mechanisms through which vascular oxidative stress develops in vivo under continuous exposure to all three of these potent arsenicals are unknown. This review is a comprehensive analysis of the mechanisms that mediate arsenic effects associated with Nox2 activation, ROS activity, and endothelial dysfunction, and also considers future avenues of research into what is a relatively poorly understood topic with major implications for human health.
authors: Bristol Heart Institute, University of Bristol, Bristol, United Kingdom davidellinsworth@gmail.com.
authors: David C
authors: DC
authors: Ellinsworth
mesh_terms: D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D020261:Arsenic Poisoning / Q000503:physiopathology*; D060766:Drinking Water; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014652:Vascular Diseases / Q000139:chemically induced* / Q000503:physiopathology
chemical_list: D060766:Drinking Water; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D001151:Arsenic