Efeitos da exposição crônica ao cloreto de mercúrio (HgCl2) sobre a reatividade vascular e propriedades mecânicas e estruturais de artérias de resistência de ratos

• Ano de defesa: 2008
• Autor(a) principal: Peçanha, Giulia Alessandra Wiggers
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal do Espírito Santo; BR; Doutorado em Ciências Fisiológicas; Centro de Ciências da Saúde; UFES; Programa de Pós-Graduação em Ciências Fisiológicas
• Palavras-chave em Português: Cloreto de Mercúrio; Reatividade; Estrutura; Artérias de Resistência; Fisiologia; 612
• Link de acesso: http://repositorio.ufes.br/handle/10/5158

Mercury produces toxic effects in both central nervous system and kidneys but its cardiovascular effects are not well explored yet. Among the toxicity mechanisms suggested an increase of oxidative stress has been proposed. This study analyzed the effects of chronic exposition to low concentrations of HgCl2 in endothelium-dependent responses of resistance arteries. Mesenteric resistance (MRA) and basilar arteries from 3-month old Wistar rats daily treated with HgCl2 (1st dose 1.3 µg, subsequent doses 0.02 µg, i.m) or vehicle by 30 days were used. Plasma mercury levels were determinated by Atomic Absorption Spectrometry and systolic blood pressure (SBP) by tail cuff. Vascular reactivity and structure of arteries were studied by wire myography and pressure myography respectively. Protein expression was evaluated by Western Blot and gene expression by RT-PCR. Superoxide anion (O2 •- ) levels were determined by dihydroethidium fluorescence, plasmatic malondialdehyde (MDA) levels by thiobarbituric acid assay and total antioxidant status by a commercial kit. Mercury plasmatic levels after 30 days of treatment were 29.2 ± 2.15 nM. Mercury treatment did not affect SBP, but increased phenylephrine contractile response, reduced acetylcholine (ACh)-induced vasodilatation and did not change the vasodilatation to the nitric oxide donor DEA-NO (10 nM-10 µM) in MRA. Mercury treatment also increased serotonin (5-HT) contractile response in basilar arteries. Endothelium removal and the NO synthase inhibitor (L-NAME, 100 µM) increased phenylephrine response only in control rats. Coincubation with L-NAME plus superoxide dismutase (SOD, 150 U/ml) on the HgCl2 group restored the effect of L-NAME in contractile response to phenylephrine and the SOD reversed the HgCl2 effect in basilar arteries. SOD, the hydrogen peroxide scavenger, catalase (1000 U/ml) or the NADPH oxidase inhibitor, apocynin (0.3 mM) restored the impaired ACh-induced vasodilatation in treated rats. The incubation with TEA, an inhibitor of K+ channels, increased the sensitivity to phenylephrine in control but did not modify the response in HgCl2 group. Indomethacin and tranilcipromine incubation did not alter the sensivity or maximum response to phenylephrine. Vascular superoxide anion production, eNOS expression, plasmatic MDA levels and total antioxidant status increased by HgCl2 treatment. However, SOD isoforms expression, COX and NOX gene expression remained unchanged. The HgCl2 treatment reduced the MRA wall thickness but increased its lumen diameter. These results suggest the chronic administration of low concentrations of HgCl2 increases the vascular reactivity to phenylephrine/serotonin, promotes endothelial dysfunction and alters the structure of MRA. This impairment of vascular function seems to be due to NO decreased bioavailability by increased O2 production from NADPH oxidase.