dc.contributor.author | Simões, Maylla Ronacher | |
dc.contributor.author | Aguado, Andrea | |
dc.contributor.author | Fiorim, Jonaína | |
dc.contributor.author | Silveira, Edna Aparecida | |
dc.contributor.author | Azevedo, Bruna Fernandes | |
dc.contributor.author | Toscano, Cindy Medice | |
dc.contributor.author | Zhenyukh, Olha | |
dc.contributor.author | Briones Alonso, Ana María | |
dc.contributor.author | Alonso, María Jesús | |
dc.contributor.author | Vassallo, Dalton Valentim | |
dc.contributor.author | Salaices Sánchez, Mercedes | |
dc.contributor.other | UAM. Departamento de Farmacología | es_ES |
dc.contributor.other | Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ) | es_ES |
dc.date.accessioned | 2016-05-30T11:54:58Z | |
dc.date.available | 2016-05-30T11:54:58Z | |
dc.date.issued | 2015-03-01 | |
dc.identifier.citation | Toxicology and applied pharmacology 283.2 (2015): 127-138 | en_US |
dc.identifier.issn | 0041-008X | es_ES |
dc.identifier.issn | 1096-0333 (on line) | es_ES |
dc.identifier.uri | http://hdl.handle.net/10486/671131 | |
dc.description.abstract | Chronic exposure to low lead concentration produces hypertension; however, the underlying mechanisms remain unclear. We analyzed the role of oxidative stress, cyclooxygenase-2-dependent pathways and MAPK in the vascular alterations induced by chronic lead exposure. Aortas from lead-treated Wistar rats (1st dose: 10 μg/100 g; subsequent doses: 0.125 μg/100 g, intramuscular, 30 days) and cultured aortic vascular smooth muscle cells (VSMCs) from Sprague Dawley rats stimulated with lead (20 μg/dL) were used. Lead blood levels of treated rats attained 21.7 ± 2.38 μg/dL. Lead exposure increased systolic blood pressure and aortic ring contractile response to phenylephrine, reduced acetylcholine-induced relaxation and did not affect sodium nitroprusside relaxation. Endothelium removal and L-NAME left-shifted the response to phenylephrine more in untreated than in lead-treated rats. Apocynin and indomethacin decreased more the response to phenylephrine in treated than in untreated rats. Aortic protein expression of gp91(phox), Cu/Zn-SOD, Mn-SOD and COX-2 increased after lead exposure. In cultured VSMCs lead 1) increased superoxide anion production, NADPH oxidase activity and gene and/or protein levels of NOX-1, NOX-4, Mn-SOD, EC-SOD and COX-2 and 2) activated ERK1/2 and p38 MAPK. Both antioxidants and COX-2 inhibitors normalized superoxide anion production, NADPH oxidase activity and mRNA levels of NOX-1, NOX-4 and COX-2. Blockade of the ERK1/2 and p38 signaling pathways abolished lead-induced NOX-1, NOX-4 and COX-2 expression. Results show that lead activation of the MAPK signaling pathways activates inflammatory proteins such as NADPH oxidase and COX-2, suggesting a reciprocal interplay and contribution to vascular dysfunction as an underlying mechanisms for lead-induced hypertension | en_US |
dc.description.sponsorship | This work was supported by MINECO (SAF2012-36400), ISCIII
7 (RD12/0042/0024), PRONEX-CNPq/FAPES (48511935/2009). MRS was a
8 fellow of CAPES and CNPq. AMB was supported by the Ramon y Cajal
9 Program (RyC2010-06473). | es_ES |
dc.format.extent | 50 pag. | es_ES |
dc.format.mimetype | application/pdf | en |
dc.language.iso | eng | en |
dc.publisher | Elsevier Inc. | es_ES |
dc.relation.ispartof | Toxicology and Applied Pharmacology | en |
dc.rights | © 2015 Elsevier Inc | es_ES |
dc.subject.other | Blood pressure | en_US |
dc.subject.other | Cyclooxygenase-2 | en_US |
dc.subject.other | Lead exposure | en_US |
dc.subject.other | MAPK pathway | en_US |
dc.subject.other | Oxidative stress | en_US |
dc.subject.other | Vascular reactivity | en_US |
dc.title | MAPK pathway activation by chronic lead-exposure increases vascular reactivity through oxidative stress/cyclooxygenase-2-dependent pathways | en_US |
dc.type | article | en |
dc.subject.eciencia | Farmacia | es_ES |
dc.relation.publisherversion | http://dx.doi.org/10.1016/j.taap.2015.01.005 | es_ES |
dc.identifier.doi | 10.1016/j.taap.2015.01.005 | es_ES |
dc.identifier.publicationfirstpage | 127 | es_ES |
dc.identifier.publicationissue | 2 | es_ES |
dc.identifier.publicationlastpage | 138 | es_ES |
dc.identifier.publicationvolume | 283 | es_ES |
dc.relation.projectID | Gobierno de España. SAF2012-36400 | es_ES |
dc.type.version | subittedVersion | en_US |
dc.rights.accessRights | openAccess | en |
dc.authorUAM | Bríones Alonso, Ana María (263298) | |
dc.authorUAM | Salaices Sánchez, Mercedes (260920) | |
dc.facultadUAM | Facultad de Medicina | |
dc.institutoUAM | Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ) | |