Apocynin Prevents Vascular Effects Caused by Chronic Exposure to Low Concentrations of Mercury.docVIP

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Apocynin Prevents Vascular Effects Caused by Chronic Exposure to Low Concentrations of Mercury.doc

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Apocynin Prevents Vascular Effects Caused by Chronic Exposure to Low Concentrations of Mercury

ApocyninPreventsVascularEffectsCausedbyChronic ExposuretoLowConcentrationsofMercury DanizeA.Rizzetti1,Joa?oGuilhermeD.Torres1,AlyneG.Escobar1,FranckM.Pec?anha1, FrancielliW.Santos1,RobsonL.Puntel1,Mar?′aJ.Alonso3,AnaM.Briones4,MercedesSalaices4, DaltonV.Vassallo2,GiuliaA.Wiggers1* 1PostgraduatePrograminBiochemistry,UniversidadeFederaldoPampa,Uruguaiana,RS,Brazil,2DepartmentofPhysiologicalSciences,UniversidadeFederaldoEsp?′rito Santo,Vito′ria,ES,Brazil,3DepartmentofBiochemistry,PhysiologyandMolecularGenetics,UniversidadReyJuanCarlos,Alcorco′n,Spain,4DepartmentofPharmacology, SchoolofMedicine,UniversidadAuto′nomadeMadrid,Madrid,Spain 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 investigatewhethertreatmentwithapocynin,anNADPHoxidaseinhibitor,preventsthevasculareffectscausedbychronic intoxication with low concentrations of mercury. Three-month-old male Wistar rats were treated for 30 days with a) intramuscularinjections(i.m.)ofsaline;b)HgCl2(i.m.1stdose:4.6mg/kg,subsequentdoses:0.07mg/kg/day);c)Apocynin (1.5mMindrinkingwaterplussalinei.m.);andd)ApocyninplusHgCl2.Themercurytreatmentresultedin1)anincreased aorticvasoconstrictorresponsetophenylephrineandreducedendothelium-dependentresponsestoacetylcholine;2)the increasedinvolvementofROSandvasoconstrictorprostanoidsinresponsetophenylephrine,whereastheendothelialNO 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 preventedtheincreasedphenylephrineresponsesandreducedtheendothelialdysfunctionelicitedbymercurytreatment. In addition, apoc