Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

Kesavan, Manickam; Sarath, T.; Kandasamy, Kannan; Suresh, Subramaniyam; Gupta, Priyanka; Vijayakaran, Karunakaran; Sankar, P.; Kurade, N. P.; Mishra, Santosh Kumar; Sarkar, Srobana

doi:10.1016/j.taap.2014.07.008

Cited by 39 publications

(23 citation statements)

References 57 publications

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“…We observed a significant reduction in the left ventricular systolic function in HF patients, which in turn significantly decreases the LVEF. Atorvastatin is known to effectively stabilize atherosclerotic plaque, and has strong anti-oxidant and anti-inflammatory functions, which improves the ventricular remodeling and the hemodynamic stability (Kesavan et al, 2014). Therefore, atorvastatin can reverse the abnormal changes in NT-proBNP, IL-6, and IL-10 to some extent.…”

Section: Discussionmentioning

confidence: 99%

Effect of atorvastatin on plasma NT-proBNP and inflammatory cytokine expression in patients with heart failure

et al. 2015

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ABSTRACT. The aim of this study was to explore the effect of atorvastatin intervention on plasma N-terminal pro-B-type natriuretic peptide (NTproBNP) and inflammatory cytokine levels in patients with heart failure (HF). One hundred and twenty-three HF patients were selected from our hospital and randomly divided into control (N = 61) and observation (N = 62) groups; the former received conventional treatment, while the latter were given conventional treatment combined with atorvastatin. Plasma NT-proBNP, inflammatory cytokines [high-sensitive C-reactive protein (hs-CRP), interleukin (IL)-6, IL-10] and cardiac function [left ventricular enddiastolic dimension (LVEDD), left ventricular ejection fraction (LVEF), enddiastolic maximum flow rate ratio (E/A)] were compared among groups. The effective rate of treating HF significantly increased after atorvastatin treatment. The plasma NT-proBNP, IL-6, IL-10, hs-CRP, and LVEDD levels significantly decreased (P < 0.05), while the LVEF and E/A levels significantly increased (P < 0.05) in the observation group compared to the control group and before intervention. The NT-proBNP and cytokine levels significantly differed among patients with different classes of heart function (P < 0.05); the NT-proBNP and cytokine levels increased with the severity of heart function. Pearson's correlation analysis revealed a negative correlation between the NT-proBNP and inflammatory cytokine levels and LVEF and E/A values, and a positive correlation between these factors and LVEDD (P < 0.05). In conclusion, atorvastatin significantly improves cardiac function; the mechanism atorvastatin action was related to the decrease in plasma NT-proBNP and inflammatory cytokine levels.

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Section: Discussionmentioning

confidence: 99%

Effect of atorvastatin on plasma NT-proBNP and inflammatory cytokine expression in patients with heart failure

et al. 2015

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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

102

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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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“…Literature shows that to simulate the cardiovascular effects of natural arsenic exposure through drinking water in the rat model -either normal rat (50 and 100 ppm of sodium arsenite [10,11,38,39] or spontaneous hypertensive rat (100 ppm of arsenic [40]) -different concentrations of arsenic were used. In another recent study, Afolabi et al [41] exposed rats to sodium arsenite (SA) at 50, 100 and 150 ppm for 12 weeks to investigate the association between inorganic arsenic exposure through drinking water and CVDs.…”

Section: Selection Of Arsenic Concentrationmentioning

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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Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

Cited by 39 publications

References 57 publications

Effect of atorvastatin on plasma NT-proBNP and inflammatory cytokine expression in patients with heart failure

Effect of atorvastatin on plasma NT-proBNP and inflammatory cytokine expression in patients with heart failure

Arsenic, Reactive Oxygen, and Endothelial Dysfunction

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

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