Low level and sub-chronic exposure to methylmercury induces hypertension in rats: nitric oxide depletion and oxidative damage as possible mechanisms

• Published in: Archives of toxicology 2009-07, Vol.83 (7), p.653-662
• Main Authors: Grotto, Denise, de Castro, Michele M, Barcelos, Gustavo R. M, Garcia, Solange C, Barbosa, Fernando Jr
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Blood and lymphatic vessels; Blood Pressure - drug effects; Cardiology. Vascular system; Cardiovascular disease; Catalase - blood; Chemical and industrial products toxicology. Toxic occupational diseases; Environmental Health; Erythrocytes - enzymology; Glutathione - analysis; Hypertension; Hypertension - chemically induced; Hypertension - drug therapy; Inorganic Compounds; Male; Malondialdehyde - blood; Medical sciences; Mercury; Metals and various inorganic compounds; Methylmercury Compounds - pharmacology; Nitrates - blood; Nitric oxide; Nitric Oxide - blood; Nitric Oxide - metabolism; Nitrites - blood; Occupational Medicine/Industrial Medicine; Oxidation-Reduction; Oxidative Stress - drug effects; Pharmacology/Toxicology; Rats; Rats, Wistar; Rodents; Superoxide Dismutase - blood; Time Factors; Toxicology
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-009-0437-8

Increased risk of hypertension after methylmercury (MeHg) exposure has been suggested. However, the underlying mechanisms are not well explored. In this paper, we have analyzed whether sub-chronic exposure to MeHg increases systolic blood pressure even at very low levels. In addition, we analyzed if the methylmercury-induced hypertension is associated with a decreased plasmatic nitric oxide levels and with a dysregulation of the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), as well as the levels of MDA and glutathione. For this study, Wistar rats were treated with methylmercury chloride (100 μg/kg per day) or vehicle. Total treatment time was 100 days. Malondialdehyde (MDA) and circulating NOx levels and superoxide dismutase (SOD) and catalase (CAT) activities were determined in plasma, whereas glutathione levels were determined in erythrocytes. Our results show that long-term treatment at a low level of MeHg affected systolic blood pressure, increasing and reducing the levels of plasmatic MDA and NOx, respectively. However, the activity of SOD did not decrease in the MeHg exposed group when compared to the control. We found a negative correlation between plasmatic nitrite/nitrate (NOx) levels and systolic blood pressure (r = -0.67; P = 0.001), and a positive correlation between MDA and systolic blood pressure (r = 0.61; P = 0.03), thus suggesting increased inhibition of NO formation with the increase of hypertension. In conclusion, long-term exposure to a low dose of MeHg increases the systolic pressure and is associated, at least in part, with increased production of ROS as judged by increased production of malondialdehyde and depressed NO availability.