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 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.
Pi
J
J
Graduate School Doctoral Program in Medical Sciences, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
Kumagai
Y
Y
Sun
G
G
Yamauchi
H
H
Yoshida
T
T
Iso
H
H
Endo
A
A
Yu
L
L
Yuki
K
K
Miyauchi
T
T
Shimojo
N
N
D000293:Adolescent; D000328:Adult; D000368:Aged; D001149:Arsenates / Q000494:pharmacology; D001151:Arsenic / Q000032:analysis / Q000097:blood; D020261:Arsenic Poisoning / Q000097:blood* / Q000453:epidemiology*; D018053:Arsenites / Q000494:pharmacology; D002681:China / Q000453:epidemiology; D002908:Chronic Disease; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites / Q000097:blood; D014874:Water Pollutants, Chemical / Q000032:analysis / Q000097:blood
D001149:Arsenates; D018053:Arsenites; D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D014874:Water Pollutants, Chemical; D009569:Nitric Oxide; C496320:NOS1 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C015001:arsenite; D001151:Arsenic; C025657:arsenic acid