Chronic HgCl₂ treatment increases vasoconstriction induced by electrical field stimulation: role of adrenergic and nitrergic innervation

In the present study, we have investigated the possible changes in rat mesenteric artery vascular innervation function caused by chronic exposure to low doses of HgCl₂ (mercuric chloride), as well as the mechanisms involved. Rats were divided into two groups: (i) control, and (ii) HgCl₂-treated rats (30 days; first dose, 4.6 μg/kg of body weight; subsequent dose, 0.07 μg·kg⁻¹ of body weight·day⁻¹, intramuscularly). Vasomotor response to EFS (electrical field stimulation), NA (noradrenaline) and the NO donor DEA-NO (diethylamine NONOate) were studied, nNOS (neuronal NO synthase) and phospho-nNOS protein expression were analysed, and NO, O₂⁻ (superoxide anion) and NA release were also determined. EFS-induced contraction was higher in the HgCl₂-treated group. Phentolamine (1 μmol/l) decreased the response to EFS to a greater extent in HgCl₂-treated rats. HgCl₂ treatment increased vasoconstrictor response to exogenous NA and NA release. L-NAME (N^G-nitro-L-arginine methyl ester; 0.1 mmol/l) increased the response to EFS in both experimental groups, but the increase was greater in segments from control animals. HgCl₂ treatment decreased NO release and increased O₂⁻ production. Vasodilator response to DEA-NO was lower in HgCl₂-treated animals. Tempol increased DEA-NO-induced relaxation to a greater extent in HgCl₂-treated animals. nNOS expression was similar in arteries from both experimental groups, whereas phospho-nNOS was decreased in segments from HgCl₂-treated animals. HgCl₂ treatment increased vasoconstrictor response to EFS as a result of, in part, reduced NO bioavailability and increased adrenergic function. These findings offer further evidence that mercury, even at low concentrations, is an environmental risk factor for cardiovascular disease.