title: Low mercury concentration produces vasoconstriction, decreases nitric oxide bioavailability and increases oxidative stress in rat conductance artery.
abstract: Mercury is an environmental pollutant that reduces nitric oxide (NO) bioavailability and increases oxidative stress, having a close link with cardiovascular diseases, as carotid atherosclerosis, myocardial infarction, coronary heart disease and hypertension. One of the main sites affected by oxidative stress, which develops atherosclerosis, is the aorta. Under acute exposure to low mercury concentrations reactive oxygen species (ROS) production were only reported for resistance vessels but if low concentrations of mercury also affect conductance arteries it is still unclear. We investigated the acute effects of 6 nM HgCl(2) on endothelial function of aortic rings measuring the reactivity to phenylephrine in rings incubated, or not, with HgCl(2) for 45 min, the protein expression for cyclooxygenase 2 (COX-2) and the AT1 receptor. HgCl(2) increased Rmax and pD2 to phenylephrine without changing the vasorelaxation induced by acetylcholine and sodium nitroprusside. Endothelial damage abolished the increased reactivity to phenylephrine. The increase of Rmax and pD2 produced by L-NAME was smaller in the presence of HgCl(2). Enalapril, losartan, indomethacin, furegrelate, the selective COX-2 inhibitor NS 398, superoxide dismutase and the NADPH oxidase inhibitor apocynin reverted HgCl(2) effects on the reactivity to phenylephrine, COX-2 protein expression was increased, and AT1 expression reduced. At low concentration, below the reference values, HgCl(2) increased vasoconstrictor activity by reducing NO bioavailability due to increased ROS production by NADPH oxidase activity. Results suggest that this is due to local release of angiotensin II and prostanoid vasoconstrictors. Results also suggest that acute low concentration mercury exposure, occurring time to time could induce vascular injury due to endothelial oxidative stress and contributing to increase peripheral resistance, being a high risk factor for public health.
authors.affiliation: Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil.
authors.forename: Núbia Belem
authors.initials: NB
authors.lastname: Lemos
authors.forename: Jhuli Keli
authors.initials: JK
authors.lastname: Angeli
authors.forename: Thaís de Oliveira
authors.initials: Tde O
authors.lastname: Faria
authors.forename: Eduardo Hertel
authors.initials: EH
authors.lastname: Ribeiro
authors.forename: Dalton Valentim
authors.initials: DV
authors.lastname: Vassallo
authors.forename: Alessandra Simão
authors.initials: AS
authors.lastname: Padilha
authors.forename: Ivanita
authors.initials: I
authors.lastname: Stefanon
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000378:metabolism; D001682:Biological Availability; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D008297:Male; D008628:Mercury / Q000633:toxicity*; D019255:NADPH Oxidases / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012084:Renin-Angiotensin System; D013482:Superoxide Dismutase / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D005609:Free Radicals; D017382:Reactive Oxygen Species; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D008628:Mercury; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester