Apocynin prevents vascular effects caused by chronic exposure to low concentrations of mercury
Entity
UAM. Departamento de FarmacologíaPublisher
Public Library of ScienceDate
2013-02-04Citation
10.1371/journal.pone.0055806
Plos One 8.2 (2013): e55806
ISSN
1932-6203 (online)DOI
10.1371/journal.pone.0055806Funded by
This study was supported by and by grants from CAPES and CNPq/FAPES/FUNCITEC (39767531/07), Brazil, MICIIN (SAF 2009-07201, PHB2011-0001-PC), Pró-reitoria de Pesquisa (N° 20120307165228-111) – Federal University of Pampa and ISCIII (Red RECAVA RD06/0014/0011), Spain. Ana M. Briones is supported through the Ramón y Cajal program (RYC-2010-06473)Subjects
Acetophenones; Acetylcholine; Enzyme Inhibitors; Mercuric Chloride; Oxidative Stress; Prostaglandins; Tissue Culture Techniques; MedicinaRights
© 2013 Rizzetti et al.Abstract
Mercury increases the risk of cardiovascular disease and oxidative stress and alters vascular reactivity. This metal elicits endothelial dysfunction causing decreased NO bioavailability via increased oxidative stress and contractile prostanoid production. NADPH oxidase is the major source of reactive oxygen species (ROS) in the vasculature. Our aim was to investigate whether treatment with apocynin, an NADPH oxidase inhibitor, prevents the vascular effects caused by chronic intoxication with low concentrations of mercury. Three-month-old male Wistar rats were treated for 30 days with a) intramuscular injections (i.m.) of saline; b) HgCl2 (i.m. 1st dose: 4.6 μg/kg, subsequent doses: 0.07 μg/kg/day); c) Apocynin (1.5 mM in drinking water plus saline i.m.); and d) Apocynin plus HgCl2. The mercury treatment resulted in 1) an increased aortic vasoconstrictor response to phenylephrine and reduced endothelium-dependent responses to acetylcholine; 2) the increased involvement of ROS and vasoconstrictor prostanoids in response to phenylephrine, whereas the endothelial NO modulation of such responses was reduced; and 3) the reduced activity of aortic superoxide dismutase (SOD) and glutathione peroxidase (GPx) and increased plasma malondialdehyde (MDA) levels. Treatment with apocynin partially prevented the increased phenylephrine responses and reduced the endothelial dysfunction elicited by mercury treatment. In addition, apocynin treatment increased the NO modulation of vasoconstrictor responses and aortic SOD activity and reduced plasma MDA levels without affecting the increased participation of vasoconstrictor prostanoids observed in aortic segments from mercury-treated rats. Conclusions: Mercury increases the vasoconstrictor response to phenylephrine by reducing NO bioavailability and increasing the involvement of ROS and constrictor prostanoids. Apocynin protects the vessel from the deleterious effects caused by NADPH oxidase, but not from those caused by prostanoids, thus demonstrating a two-way action
Files in this item
Google Scholar:Rizzetti, Danize A.
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Torres, João Guilherme D
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Escobar, Alyne G.
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Peçanha, Franck MacIel
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Santos, Francielli Weber
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Puntel, Robson Luiz
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Alonso, María Jesús
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Briones Alonso, Ana María
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Salaices Sánchez, Mercedes
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Vassallo, Dalton Valentim
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Wiggers, Giulia Alessandra
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