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

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 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>>
Publication Date:
Oct 01, 2014
Product 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)
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
OSTI ID:
22439857
Country of Origin:
United States
Language:
English
Other Identifying Numbers:
Journal ID: ISSN 0041-008X; CODEN: TXAPA9; Other: PII: S0041-008X(14)00267-1; TRN: US15R2988009391
Availability:
Available from http://dx.doi.org/10.1016/j.taap.2014.07.008
Submitting Site:
USN
Size:
page(s) 107-116
Announcement Date:
Mar 05, 2016

Citation Formats

Kesavan, Manickam, Sarath, Thengumpallil Sasindran, Kannan, Kandasamy, Suresh, Subramaniyam, Gupta, Priyanka, Vijayakaran, Karunakaran, Sankar, Palanisamy, Kurade, Nitin Pandurang, Mishra, Santosh Kumar, and Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com. Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators. United States: N. p., 2014. Web. doi:10.1016/J.TAAP.2014.07.008.
Kesavan, Manickam, Sarath, Thengumpallil Sasindran, Kannan, Kandasamy, Suresh, Subramaniyam, Gupta, Priyanka, Vijayakaran, Karunakaran, Sankar, Palanisamy, Kurade, Nitin Pandurang, Mishra, Santosh Kumar, & Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com. Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators. United States. doi:10.1016/J.TAAP.2014.07.008.
Kesavan, Manickam, Sarath, Thengumpallil Sasindran, Kannan, Kandasamy, Suresh, Subramaniyam, Gupta, Priyanka, Vijayakaran, Karunakaran, Sankar, Palanisamy, Kurade, Nitin Pandurang, Mishra, Santosh Kumar, and Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com. 2014. "Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators." United States. doi:10.1016/J.TAAP.2014.07.008. https://www.osti.gov/servlets/purl/10.1016/J.TAAP.2014.07.008.
@misc{etde_22439857,
title = {Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators}
author = {Kesavan, Manickam, Sarath, Thengumpallil Sasindran, Kannan, Kandasamy, Suresh, Subramaniyam, Gupta, Priyanka, Vijayakaran, Karunakaran, Sankar, Palanisamy, Kurade, Nitin Pandurang, Mishra, Santosh Kumar, and Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com}
abstractNote = {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, 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.}
doi = {10.1016/J.TAAP.2014.07.008}
journal = {Toxicology and Applied Pharmacology}
issue = {1}
volume = {280}
journal type = {AC}
place = {United States}
year = {2014}
month = {Oct}
}