shows that the mean arsenic level in the well water consumed by the 54 subjects from the end of the 1970s to August 1999 (before remediation) was 180 μg/L. In the nearly 20 years of exposure, all of the households enrolled in this study had shared between two and six of these water sources. The arsenic level of the new water supply was 37 μg/L, lower than the World Health Organization (WHO) maximum permissible limit of 50 μg/L for drinking water (WHO 1984
). The 13-month exposure reduction markedly decreased the arsenic levels in biological samples, including urine and blood samples, in a sex-independent fashion (), showing that the new low-arsenic water supply effectively reduced the body burden of arsenic.
Arsenic levels in drinking water and biological samples before and after drinking water remediation.
As shown in and , the urinary cGMP levels in all age groups of both sexes were significantly depressed before remediation when high levels of arsenic were consumed. This finding was supported by the work of Lee et al. (2003)
, who reported that arsenite can dramatically inhibit cGMP accumulation in isolated aortic rings of rats. After the 13-month arsenic exposure reduction, urinary cGMP levels increased to normal, as compared to the Japanese general population-based control values of 57.3 ± 2.1 nmol cGMP/mmol of creatinine in males (n
= 510; 40–65 years of age) and 70.6 ± 3.0 in females (n
= 622; 40–65 years of age) (Cui et al. 2004
Urinary cGMP excretion (nmol/mmol creatinine) before and after switching to low-arsenic drinking water.
Figure 1 Urinary cGMP excretion in male (n = 24) and female (n = 30) untreated chronic arsenosis patients before and after the switch to low-arsenic drinking water. Water remediation reversed the arsenic-induced suppression of cGMP production in both males (p (more ...)
In agreement with the recovery of the arsenic-induced dysfunction of the NO/cGMP system, as indicated by the increase in urinary cGMP excretion, peripheral vascular response to cold stress, measured as the difference in finger systolic blood pressure before and after ice-water immersion, was significantly improved in male arsenosis patients (). In female arsenosis patients, although some improvement in finger blood pressure response occurred, it was not statistically significant (). The difference between peripheral vascular response to cold stress between male and female patients before remediation was also significant (), which is consistent with more severe exposure in males as evidenced by blood and urinary arsenic () and skin lesions. In addition, 3 of the 16 patients reporting cold-weather–associated pain and coldness and/or white fingers showed improvement, although 12 patients had no significant change, and 1 patient became worse (data not shown).
Peripheral vascular response to cold stress before and after switching to low-arsenic drinking water.
Replacement of drinking water heavily contaminated with arsenic with low-arsenic water is a potential intervention strategy to minimize or reverse the adverse health effects of this toxic inorganic element. Consistent with our previous results (Pi et al. 2000
), male and female arsenosis patients in the present study showed a marked depression in urinary excretion of cGMP, and a 13-month period of consuming low-arsenic drinking water reversed this depression. In addition, improved peripheral vascular response to cold stress was clearly observed in male arsenosis patients after consuming low-arsenic water and tended to improve in females. Together, these data suggest that long-term arsenic exposure induces biochemical changes in the vascular system and causes functional vascular damage, which, at least in males, can be reversed by limiting further arsenic intake. Although cGMP production improved, it is possible that females may need a longer period of reduced arsenic exposure for vascular function to be completely restored. In addition, before remediation, males had much higher blood and urinary arsenic levels and showed a higher rate of arsenic-induced skin lesions, indicating more severe intoxication. Thus, improvement of the symptoms of arsenic poisoning may be more readily observed in males.
In conclusion, a 13-month arsenic exposure reduction effectively reverses the arsenic-induced impairment of the NO/cGMP pathway in both males and females and improves peripheral vascular function in males. Additional comprehensive follow-up studies are necessary to document the long-term health benefits of arsenic exposure reduction, but the present results indicate the reduction of arsenic exposure could be an important public health strategy.