Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

Sarath, T.; Waghe, Prashantkumar; Gupta, Priyanka; Choudhury, Soumen; Kandasamy, Kannan; Pillai, Harikrishna; Harikumar, S.; Mishra, Santosh Kumar; Sarkar, Srobana

doi:10.1016/j.taap.2014.08.032

Cited by 40 publications

(25 citation statements)

References 60 publications

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“…However, although exposure of rats chronically to drinking water containing extremely high concentrations (100 mg/l) of As III modulates aortic eNOS phosphorylation and expression (Kesavan et al, 2014;Sarath et al, 2014), it is currently unclear whether environmentally relevant levels of As III evoke similar effects in vivo. Indeed, in human aortic ECs treated with 100 mg/l As 2 O 3 (equating to ∼0.5 mmol/l) reductions in NO bioavailability (observed after 1-hour incubation) are followed by decreased activity and downregulation of eNOS (after 72-hour exposure), but although the authors of this study investigated the significance of these findings in rats in vivo, neither serum NO metabolites nor aortic eNOS content were affected (Chou et al, 2007).…”

Section: Implies That Omentioning

confidence: 99%

Arsenic, Reactive Oxygen, and Endothelial Dysfunction

Ellinsworth

2015

J Pharmacol Exp Ther

104

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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.

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Section: Implies That Omentioning

confidence: 99%

Arsenic, Reactive Oxygen, and Endothelial Dysfunction

Ellinsworth

2015

J Pharmacol Exp Ther

104

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“…Epidemiological studies reported increased incidence of hypertension in arsenic-exposed populations [7][8][9]. Further, evidences showed that arsenic induced hypertension in rats [10,11] and mice [12].…”

Section: Introductionmentioning

confidence: 98%

“…Hossain et al [18] also showed that the arsenic-induced AT 1 R up-regulation was due to generation of reactive oxygen species (ROS). Arsenite stimulated NADPH oxidase (Nox) of endothelial cells, VSMCs and thoracic aorta causing increased generation of ROS [10,20,21], which activated mitogen activated protein kinase (MAPK) signaling pathways and resulted in vascular endothelial growth factor (VEGF) over-expression [22]. The stress inducer arsenic (sodium arsenite) was shown to activate members of the MAPK family in different cell lines [23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Arsenic causes aortic dysfunction and systemic hypertension in rats: Augmentation of angiotensin II signaling

Waghe

Sarath

Gupta

et al. 2015

Chemico-Biological Interactions

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“…Among its pleiotropic functions, atorvastatin has been reported to improve endothelial function through increased bioavailability of NO and ameliorated ROS and pro-inflammatory cytokine production in different models of hypertension [92,102,103]. Atorvastatin could lower the blood pressure of dexamethasone-treated hypertensive rats due to its positive influence on the expression of eNOS measured in aortic samples and due to the lowered levels of superoxide in plasma.…”

Section: Response To Antioxidants and Anti-inflammatory Agentsmentioning

confidence: 99%

Role of Endothelial Nitric Oxide Synthase in Glucocorticoid- Induced Hypertension: An Overview of Experimental Data

Blecharz-Lang¹,

Burek²

2017

Nitric Oxide Synthase - Simple Enzyme-Complex Roles

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Imbalances in the synthesis or in the bioavailability of nitric oxide (NO), the freely diffusible vasodilator, in myocardial endothelial cells were demonstrated to be crucial in the development of hypertension. Glucocorticoids (GCs) are widely used as immunomodulators. One of the numerous side effects of GC therapy is hypertension arising from reduced release of the endothelium-derived NO. GCs can modulate NO synthesis by targeting the genes involved in it, like nitric oxide synthase (NOS) and guanosine triphosphate (GTP) cyclohydrolase-1 (GTPCH-1). This chapter will give an overview on the impact of GCs on NO synthesis and signalling in animal models as well as in in vitro cell culture models. Moreover, strategies for preventing or neutralizing side effects of long-term GC therapy will be discussed.

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Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

Cited by 40 publications

References 60 publications

Arsenic, Reactive Oxygen, and Endothelial Dysfunction

Arsenic, Reactive Oxygen, and Endothelial Dysfunction

Arsenic causes aortic dysfunction and systemic hypertension in rats: Augmentation of angiotensin II signaling

Role of Endothelial Nitric Oxide Synthase in Glucocorticoid- Induced Hypertension: An Overview of Experimental Data

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