title: Chronic mercury exposure at different concentrations produces opposed vascular responses in rat aorta.
abstract: Mercury chloride exposure for 30 days decreases NO bioavailability and increases oxidative stress. However, the mechanisms underlying the effects of mercury on the cardiovascular system are not completely understood, and it is not known if they are dose-dependent or if some concentrations have no harmful effects. Thus, we investigated the effects of chronic exposure to doses low (half) and high (2.5-fold higher) than that needed to obtain 29 nmol/L of HgCl2 on the vascular function. Three-month-old male Wistar rats received intramuscular (i.m.) HgCl2 for 30 days and were divided in three groups: lower (Low Hg); higher (High Hg); and saline was used as the control. High Hg exposure increased the contractile response to phenylephrine (PHE) in aortic rings, but Low Hg reduced it. The hyporesponsiveness in the Low Hg rats was blunted by endothelial denudation and NOS inhibition with l-NAME (100 μmol/L). The phosphorylated-eNOS/eNOS protein ratio increased in the aortas of Low Hg rats. In the High Hg group, endothelial denudation increased the PHE-induced contractions, while l-NAME had no effects and indomethacin (10 μmol/L), losartan (10 μmol/L) and apocynin (30 μmol/L) reduced this response. In the High Hg group, protein levels of the NADPH oxidase subunit gp91phox and cyclooxygenase-2 increased. Our results support previous suggestions that High Hg increases oxidative stress that might activate an inflammatory cascade and the renin-angiotensin system. However, very low Hg concentrations below the level considered safe still reduced vascular reactivity, suggesting the need for special attention to continuous exposure as a putative cause of increased cardiovascular risk.
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Espirito Santo, Brazil.
authors.forename: B F
authors.initials: BF
authors.lastname: Azevedo
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Espirito Santo, Brazil.
authors.forename: M R
authors.initials: MR
authors.lastname: Simões
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Espirito Santo, Brazil.
authors.forename: J
authors.initials: J
authors.lastname: Fiorim
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Espirito Santo, Brazil.
authors.forename: T
authors.initials: T
authors.lastname: Botelho
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Espirito Santo, Brazil.
authors.forename: J K
authors.initials: JK
authors.lastname: Angeli
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Espirito Santo, Brazil.
authors.forename: Jva
authors.initials: J
authors.lastname: Vieira
authors.affiliation: Department of Ciencias Básicas de la Salud, Universidad Rey Juan Carlos, Alcorcón, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Alonso
authors.affiliation: Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Salaices
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Espirito Santo, Brazil.
authors.forename: L
authors.initials: L
authors.lastname: Dos Santos
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Espirito Santo, Brazil.|Health Science of Vitória-EMESCAM, Vitória, Espirito Santo, Brazil.
authors.forename: D V
authors.initials: DV
authors.lastname: Vassallo
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008627:Mercuric Chloride / Q000009:adverse effects; D008628:Mercury / Q000009:adverse effects*; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D008627:Mercuric Chloride; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; D008628:Mercury
keywords: endothelial function; heavy metal; mercuric chloride; oxidative stress; vascular reactivity