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

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 drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91{sup st} 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 adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited E{sub max} 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 acetylcholine-induced 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,more » 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. - Highlights: • We evaluated if atorvastatin reduce arsenic-induced vascular dysfunction. • Arsenic reduced ACh-induced aortic relaxation but didn’t alter response to SNP and PE. • Arsenic affected aortic NO signalling and production of inflammatory mediators. • Arsenic produced vasculopathic lesions in aorta. • Atorvastatin restored arsenic-induced functional, biochemical and structural changes.« less
Authors:
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Publication Date:
OSTI Identifier:
22439857
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 280; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACETYLCHOLINE; ADHESION; AORTA; ARSENIC; CARDIOVASCULAR DISEASES; DRINKING WATER; ECOLOGICAL CONCENTRATION; ENZYME IMMUNOASSAY; GLOBULINS; GUANOSINE; HAZARDS; INFLAMMATION; MESSENGER-RNA; MONOCYTES; NITRIC OXIDE; PHOSPHORYLATION; RATS; RELAXATION