Exposição a baixa concentração de HgCl2 durante 30 dias deprime a contratilidade miocárdica e promove disfunção coronariana em ratos
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2011-11-25
Autores
Furieri, Lorena Barros
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Universidade Federal do Espírito Santo
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Exposure to mercury is known to increase cardiovascular risk but the underlying mechanisms are not well explored. We analysed whether chronic exposure to low mercury doses affects endothelial modulation of the coronary circulation and cardiac function. Left coronary arteries and hearts from male Wistar rats treated with either HgCl2 (first dose 4.6 mg·kg-1, subsequent doses 0.07 mg·kg-1 day-1, 30 days IM) or vehicle were used. Endothelial cells from pig coronary arteries incubated with HgCl2 were also used. Mercury treatment increased 5-HT-induced vasoconstriction but reduced acetylcholine-induced vasodilatation. It also reduced nitric oxide (NO) production and the effects of NO synthase inhibition with L-NAME (100 mmol/L) on 5-HT and acetylcholine responses. Superoxide anion production and mRNA levels of NOX-1 and NOX-4 were all increased. The superoxide anion scavenger tiron (1 mmol/L) and SOD (150 U/mL) reduced 5-HT responses only in vessels from mercury-treated rats. Tiron (1 mmol/L) and apocynin (0.3 mmol/L) increased acetylcholine responses in treated group. In mercury-treated coronary arteries SOD-2 mRNA level was increased. The inhibitor of COX, indomethacin (10 µmol/L), decreased 5-HT responses and increased acetylcoline responses in treated group. Also, the inhibitor of calciumdependent potassium channels, TEA (2 mmol/L), enhanced 5-HT responses in mercury exposure animals. In isolated hearts from mercury-treated rats, coronary perfusion and diastolic pressure were unchanged, but developed isovolumetric systolic pressure was reduced. In these hearts, L-NAME increased coronary perfusion pressure and diastolic pressure, while it further reduced developed systolic pressure. Also, reduced protein expression of SERCA and phosphorylated phospholamban on serine 16 while phospholamban expression increased; as a consequence SERCA/phospholamban ratio reduced; reduced sodium/calcium exchanger (NCX) protein expression and α-1 isoform of NKA, whereas α-2 isoform of NKA did not change; cardiac eNOS and iNOS were reduced. Chronic exposure to low doses of mercury promotes endothelial dysfunction of coronary arteries, as shown by decreased NO bioavailability induced by increased oxidative stress. These effects on coronary function increase resistance to flow, which under overload conditions might cause ventricular contraction and relaxation impairment. These findings provide further evidence that mercury, even at low doses, could be an environmental risk factor for cardiovascular disease.
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FURIERI, Lorena Barros. Exposição a baixa concentração de HgCl2 durante 30 dias deprime a contratilidade miocárdica e promove disfunção coronariana em ratos. 2018. Tese (Doutorado em Ciências Fisiológicas) — Universidade Federal do Espírito Santo, Centro de Ciências da Saúde, Vitória, 2011.