Pi J, Kumagai Y, Sun G, Yamauchi H, Yoshida T, Iso H, Endo A, Yu L, Yuki K, Miyauchi T, Shimojo N
Graduate School Doctoral Program in Medical Sciences, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
Free Radic Biol Med. 2000 Apr 1;28(7):1137-42. doi: 10.1016/s0891-5849(00)00209-4.
Prolonged exposure to arsenic results in peripheral and cardiovascular manifestations, as does impaired production of endothelial nitric oxide (NO). In vitro studies have indicated that endothelial cells undergo damage by arsenic. However, no information has been available on the relationship between NO synthesis and chronic arsenic poisoning in humans. The present study was designed to reveal this question. The subjects were 33 habitants who continued to drink well water containing high concentrations of inorganic arsenic (mean value = 0.41 microg/ml) for about 18 years in Inner Mongolia, China, and 10 other people who lived in this area but exposed to minimal concentrations of arsenic (mean value = 0.02 microg/ml) were employed as controls. Mean blood concentration of total arsenic was six times higher in exposed subjects 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 arsenic-exposed subjects than in controls: 24.7 vs. 51.6 microM, p<.001. In total samples, an inverse correlation with serum nitrite/nitrate levels was strong for blood inorganic arsenic (r = -0.52, p <.001) and less strong for its metabolites, monomethyl arsenic (r = -0.45, p<.005) and dimethyl arsenic (r = -0.37, p<.05). Furthermore, serum nitrite/nitrate concentration was significantly correlated with nonprotein sulfhydryl level in whole blood (r = 0.58, p<.001). In an in vitro study, we demonstrated that inorganic arsenite or arsenate suppresses the activity of endothelial NO synthase in human umbilical vein endothelial cells. These results suggest that long-term exposure to arsenic by drinking well water possibly reduces NO production in endothelial cells, resulting in a decrease in reduced nitrite/nitrate concentrations. Peripheral vascular disorders caused by arsenic may be attributable in part to impairment of NO production in vivo.
长期接触砷会导致外周和心血管方面的表现，内皮一氧化氮（NO）生成受损也会如此。体外研究表明，内皮细胞会受到砷的损害。然而，关于人体中NO合成与慢性砷中毒之间的关系尚无相关信息。本研究旨在揭示这一问题。研究对象为中国内蒙古33名居民，他们持续饮用含高浓度无机砷（平均值 = 0.41微克/毫升）的井水约18年，另外选取10名居住在该地区但接触极低浓度砷（平均值 = 0.02微克/毫升）的居民作为对照。砷暴露组受试者的总砷平均血浓度比对照组高6倍：分别为42.1纳克/毫升和7.3纳克/毫升，p <.001。砷暴露组受试者内源性NO的稳定代谢产物亚硝酸盐/硝酸盐的平均血清浓度低于对照组：分别为24.7微摩尔/升和51.6微摩尔/升，p<.001。在所有样本中，血液无机砷与血清亚硝酸盐/硝酸盐水平呈强负相关（r = -0.52，p <.001），其代谢产物一甲基砷（r = -0.45，p<.005）和二甲基砷（r = -0.37，p<.05）的相关性则较弱。此外，血清亚硝酸盐/硝酸盐浓度与全血中非蛋白巯基水平显著相关（r = 0.58，p<.001）。在一项体外研究中，我们证明无机亚砷酸盐或砷酸盐会抑制人脐静脉内皮细胞中内皮型一氧化氮合酶的活性。这些结果表明，长期饮用井水接触砷可能会降低内皮细胞中NO的生成，导致亚硝酸盐/硝酸盐还原浓度降低。砷引起的外周血管疾病可能部分归因于体内NO生成受损。
