Decreased serum concentrations of nitric oxide metabolites among Chinese in an endemic area of chronic arsenic poisoning in Inner Mongolia

Prolonged exposure to arsenic results in peripheral and cardiovascular mani festations, as does impaired production of endothelial nitric oxide (NO). I n vitro studies have indicated that endothelial cells undergo damage by ars enic. However, no information has been available on the relationship betwee n NO synthesis and chronic arsenic poisoning in humans. The present study w as designed to reveal this question. The subjects were 33 habitants who con tinued to drink well water containing high concentrations of inorganic arse nic (mean value = 0.41 mu g/ml) for about 18 years in Inner Mongolia, China , and 10 other people who lived in this area but exposed to minimal concent rations of arsenic (mean value = 0.02 mu g/ml) were employed as controls. M ean blood concentration of total arsenic was six times higher in exposed su bjects than controls; 42.1 vs. 7.3 ng/ml, p <.001. Mean serum concentration of nitrite/nitrate, stable metabolites of endogenous NO, was lower in arse nic-exposed subjects than in controls: 24.7 vs. 51.6 mu M, p < .001. In tot al samples, an inverse correlation with serum nitrite/nitrate levels was st rong for blood inorganic arsenic (r = -0.52, p < .001) and less strong for its metabolites, monomethyl arsenic (r = -0.45, p < .005) and dimethyl arse nic (r = -0.37, p < .05). Furthermore, serum nitrite/nitrate concentration was significantly correlated with nonprotein sulfhydryl level in whole bloo d (r = 0.58, p < .001). In an in vitro study, we demonstrated that inorgani c arsenite or arsenate suppresses the activity of endothelial NO synthase i n human umbilical vein endothelial cells. These results suggest that long-t erm exposure to arsenic by drinking well water possibly reduces NO producti on in endothelial cells, resulting in a decrease in reduced nitrite/nitrate concentrations. Peripheral vascular disorders caused by arsenic may be att ributable in part to impairment of NO production in vivo. (C) 2000 Elsevier Science Inc.