Low level and sub-chronic exposure to methylmercury induces hypertension in rats: nitric oxide depletion and oxidative damage as possible mechanisms.
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 microg/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.
Grotto
Denise
D
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP 14040-903, Brazil.
de Castro
Michele M
MM
Barcelos
Gustavo R M
GR
Garcia
Solange C
SC
Barbosa
Fernando
F
D000818:Animals; D000975:Antioxidants; D001794:Blood Pressure / Q000187:drug effects; D002374:Catalase / Q000097:blood; D004912:Erythrocytes / Q000201:enzymology; D005978:Glutathione / Q000032:analysis; D006973:Hypertension / Q000139:chemically induced* / Q000188:drug therapy*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008767:Methylmercury Compounds / Q000494:pharmacology*; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood* / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000097:blood; D013997:Time Factors
D000975:Antioxidants; D008767:Methylmercury Compounds; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D008315:Malondialdehyde; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; C004925:methylmercuric chloride