title: Cerebrovascular endothelial dysfunction induced by mercury exposure at low concentrations.
abstract: Mercury (Hg) has many harmful vascular effects by increasing oxidative stress, inflammation and vascular/endothelial dysfunction, all of which may contribute to cerebrovascular diseases development. We aimed to explore the effects of chronic low-mercury concentration on vascular function in cerebral arteries and the mechanisms involved. Basilar arteries from control (vehicle-saline solution, im) and mercury chloride (HgCl2)-treated rats for 30 days (first dose 4.6μg/kg, subsequent dose 0.07μg/kg/day, im, to cover daily loss) were used. Vascular reactivity, protein expression, nitric oxide (NO) levels and superoxide anion (O2(-)) production were analyzed. HgCl2 exposure increased serotonin contraction and reduced the endothelium-dependent vasodilatation to bradykinin. After NO synthase inhibition, serotonin responses were enhanced more in control than in mercury-treated rats while bradykinin-induced relaxation was abolished. NO levels were greater in control than Hg-treated rats. Tiron and indomethacin reduced vasoconstriction and increased the bradykinin-induced relaxation only in HgCl2-treated rats. Vascular O2(-) production was greater in mercury-treated when compared to control rats. Protein expressions of endothelial NO synthase, copper/zinc (Cu/Zn), Manganese (Mn) and extracellular-superoxide dismutases were similar in cerebral arteries from both groups. Results suggest that Hg treatment increases cerebrovascular reactivity by reducing endothelial negative modulation and NO bioavailability; this effect seems to be dependent on increased reactive oxygen species and prostanoids generation. These findings show, for the first time, that brain vasculature are also affected by chronic mercury exposure and offer further evidence that even at small concentration, HgCl2 is hazardous and might be an environmental risk factor accounting for cerebral vasospasm development.
authors.affiliation: Postgraduate Program in Biochemistry, Universidade Federal do Pampa, Rio Grande do Sul, Unipampa, Campus Uruguaiana, BR 472, km 592, PO Box 118, Uruguaiana, RS 97500-970, Brazil; Department of Pharmacology, School of Medicine, Universidad Autónoma de Madrid, Calle Arzobispo Morcillo s/n, 28029 Madrid, Spain. Electronic address: giuliawp@gmail.com.
authors.forename: Giulia Alessandra
authors.initials: GA
authors.lastname: Wiggers
authors.affiliation: Department of Physiological Sciences, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Avenida Marechal Campos, 1468, Vitória, ES 29040-090, Brazil; Department of Pharmacology, School of Medicine, Universidad Autónoma de Madrid, Calle Arzobispo Morcillo s/n, 28029 Madrid, Spain. Electronic address: lorena.furieri@ufes.br.
authors.forename: Lorena Barros
authors.initials: LB
authors.lastname: Furieri
authors.affiliation: Department of Pharmacology, School of Medicine, Universidad Autónoma de Madrid, Calle Arzobispo Morcillo s/n, 28029 Madrid, Spain. Electronic address: ana.briones@uam.es.
authors.forename: Ana María
authors.initials: AM
authors.lastname: Briones
authors.affiliation: Department of Pharmacology, School of Medicine, Universidad Autónoma de Madrid, Calle Arzobispo Morcillo s/n, 28029 Madrid, Spain. Electronic address: marisol.avendanno@uam.es.
authors.forename: María Soledad
authors.initials: MS
authors.lastname: Avendaño
authors.affiliation: Postgraduate Program in Biochemistry, Universidade Federal do Pampa, Rio Grande do Sul, Unipampa, Campus Uruguaiana, BR 472, km 592, PO Box 118, Uruguaiana, RS 97500-970, Brazil; Department of Pharmacology, School of Medicine, Universidad Autónoma de Madrid, Calle Arzobispo Morcillo s/n, 28029 Madrid, Spain.
authors.forename: Franck Maciel
authors.initials: FM
authors.lastname: Peçanha
authors.affiliation: Department of Physiological Sciences, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Avenida Marechal Campos, 1468, Vitória, ES 29040-090, Brazil. Electronic address: daltonv2@terra.com.br.
authors.forename: Dalton Valentim
authors.initials: DV
authors.lastname: Vassallo
authors.affiliation: Department of Pharmacology, School of Medicine, Universidad Autónoma de Madrid, Calle Arzobispo Morcillo s/n, 28029 Madrid, Spain. Electronic address: mercedes.salaices@uam.es.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Salaices
authors.affiliation: Department of Ciencias Básicas de la Salud, Universidad Rey Juan Carlos, Avenida de Atenas s/n, 28922 Alcorcón, Madrid, Spain. Electronic address: mariajesus.alonso@urjc.es.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Alonso
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001488:Basilar Artery / Q000166:cytology; D001835:Body Weight / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D002561:Cerebrovascular Disorders / Q000139:chemically induced* / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects*; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D008627:Mercuric Chloride / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D006834:Hydrazines; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D013481:Superoxides; D009569:Nitric Oxide; D012701:Serotonin; D008627:Mercuric Chloride; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester
keywords: Cerebral arteries; Mercury; Reactive oxygen species; Vascular reactivity and prostanoids