Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators
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Date
2014
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Abstract
We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases,
can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the
modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite
(100 ppm)through drinkingwater for 90 consecutive days. Atorvastatin (10 mg/kgbw, orally)was administered
once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for measuring serum
C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside
and acetylcholine; evaluating eNOS and iNOS mRNA expression and measuring NO production,while abdominal
aorta was used for ELISA of cytokines, chemokine and vascular cell adhesionmolecules. Histopathologywas done
in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited Emax of phenylephrine,
but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium
nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholineinduced
relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation
and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis,
production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein
and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and
structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular
dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating
production of pro-inflammatory mediators and cell adhesion molecules.
Description
TNV_TAP_2014_280(107-116)
Keywords
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