Endothelial dysfunction of rat coronary arteries after exposure to low concentrations of mercury is dependent on reactive oxygen species

• Published in: British journal of pharmacology Vol. 162; no. 8; pp. 1819 - 1831
• Main Authors: Furieri, Lorena B, Galán, María, Avendaño, María S, García‐Redondo, Ana B, Aguado, Andrea, Martínez, Sonia, Cachofeiro, Victoria, Bartolomé, M Visitación, Alonso, María J, Vassallo, Dalton V, Salaices, Mercedes
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-04-2011; Nature Publishing Group
• Subjects: Animals; Biological and medical sciences; Blood Pressure - drug effects; coronary arteries; Coronary Vessels - drug effects; Coronary Vessels - pathology; endothelial dysfunction; Endothelium, Vascular - drug effects; Endothelium, Vascular - pathology; Male; Medical sciences; Mercuric Chloride - administration & dosage; Mercuric Chloride - toxicity; mercury; Nitric Oxide - metabolism; oxidative stress; Oxidative Stress - drug effects; Pharmacology. Drug treatments; Rats; Rats, Wistar; Reactive Oxygen Species - metabolism; Research Papers; Swine; Vasoconstriction - drug effects; Vasodilation - drug effects; Oxidative stress; Reactive oxygen species; Rat; Rodentia; Coronary artery; Heavy metal; Vertebrata; Mammalia; coronary arteries; Animal; Blood vessel; Endothelial dysfunction; Circulatory system; Mercury
• ISSN: 0007-1188; 1476-5381; 1476-5381
• DOI: 10.1111/j.1476-5381.2011.01203.x

BACKGROUND AND PURPOSE 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.
EXPERIMENTAL APPROACH Left coronary arteries and hearts from Wistar rats treated with either HgCl2 (first dose 4.6 µg·kg−1, subsequent doses 0.07 µg·kg−1 day−1, 30 days) or vehicle were used. Endothelial cells from pig coronary arteries incubated with HgCl2 were also used.
KEY RESULTS 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 µmol·L−1) 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−1) 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 IMPLICATIONS 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.