Environmental contamination has exposed humans to various metal agents, including mercury. This exposure is more common than expected, and the health consequences of such exposure remain unclear. For many years, mercury was used in a wide variety of human activities, and now, exposure to this metal from both natural and artificial sources is significantly increasing. Many studies show that high exposure to mercury induces changes in the central nervous system, potentially resulting in irritability, fatigue, behavioral changes, tremors, headaches, hearing and cognitive loss, dysarthria, incoordination, hallucinations, and death. In the cardiovascular system, mercury induces hypertension in humans and animals that has wide-ranging consequences, including alterations in endothelial function. The results described in this paper indicate that mercury exposure, even at low doses, affects endothelial and cardiovascular function. As a result, the reference values defining the limits for the absence of danger should be reduced.
BACKGROUND AND PURPOSEExposure 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.
EXPERIMENTAL APPROACHLeft coronary arteries and hearts from Wistar rats treated with either HgCl2 (first dose 4.6 mg·kg -1 , subsequent doses 0.07 mg·kg -1 day -1 , 30 days) or vehicle were used. Endothelial cells from pig coronary arteries incubated with HgCl2 were also used.
KEY RESULTSMercury 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 ) reduced 5-HT responses and increased acetylcholine responses only in vessels from mercury-treated rats. 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.
CONCLUSIONS AND IMPLICATIONSChronic 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.
AbbreviationsCPP, coronary perfusion pressure; DEA-NO, diethylamine NONOate; DHE, dihydroethidium; FITC, fluorescein isothiocyanate; KHS, Krebs-Henseleit solution; L-NAME, N-nitro-L-arginine methyl ester; LVISP, left ventricle isovolumetric systolic pressure; NOS, nitric oxide synthase; ROS, reactive oxygen species; SOD, superoxide dismutase; TEA, tetraethylammonium BJP British Journal of Pharmacology
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