BACKGROUND Hypertension is a major cause of death worldwide. Although arsenic exposure has been associated with the risk of hypertension, this association appears nonuniform due to inconsistent results from studies conducted in different populations. Moreover, hypertension is a complex condition with multiple underlying mechanisms and factors. One factor is impaired production and bioavailability of vascular nitric oxide (NO). However, the implications of the effects of arsenic exposure on circulating NO and its association with hypertension in humans are largely unknown. OBJECTIVE We investigated the dose-response relationship between arsenic exposure and hypertension with vascular NO levels as a potential mediator of arsenic-related hypertension in individuals exposed to a broad range of arsenic. METHODS A total of 828 participants were recruited from low- and high-arsenic exposure areas in Bangladesh. Participants' drinking water, hair, and nail arsenic concentrations were measured by inductively coupled plasma mass spectroscopy. Hypertension was defined as a systolic blood pressure (SBP) value of ≥140 and a diastolic (DBP) value of ≥90 mmHg. Serum NO levels reflected by total serum nitrite concentrations were measured by immunoassay. A formal causal mediation analysis was used to assess NO as a mediator of the association between arsenic level and hypertension. RESULTS Increasing concentrations of arsenic measured in drinking water, hair, and nails were associated with the increasing levels of SBP and DBP. The odds of hypertension were dose-dependently increased by arsenic even in participants exposed to relatively low to moderate levels (10-50μg/L) of water arsenic [odds ratios (ORs) and 95% confidence intervals (CIs): 2.87 (95% CI: 1.28, 6.44), 2.67 (95% CI: 1.27, 5.60), and 5.04 (95% CI: 2.71, 9.35) for the 10-50μg/L, 50.01-150μg/L, and >150μg/L groups, respectively]. Causal mediation analysis showed a significant mediating effect of NO on arsenic-related SBP, DBP, and hypertension. CONCLUSION Increasing exposure to arsenic was associated with increasing odds of hypertension. The association was mediated through the reduction of vascular NO bioavailability, suggesting that impaired NO bioavailability was a plausible underlying mechanism of arsenic-induced hypertension in this Bangladeshi population. https://doi.org/10.1289/EHP13018.

中文翻译：

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孟加拉国与砷暴露相关的高血压和循环一氧化氮生物利用度降低。


背景技术高血压是全世界死亡的主要原因。尽管砷暴露与高血压风险相关，但由于在不同人群中进行的研究结果不一致，这种关联似乎不均匀。此外，高血压是一种复杂的疾病，具有多种潜在机制和因素。其中一个因素是血管一氧化氮 (NO) 的产生和生物利用度受损。然而，砷暴露对循环一氧化氮的影响及其与人类高血压的关系尚不清楚。目的 我们研究了砷暴露与高血压之间的剂量反应关系，血管一氧化氮水平是暴露于各种砷的个体中与砷相关的高血压的潜在介质。方法 从孟加拉国低砷和高砷暴露地区总共招募了 828 名参与者。通过电感耦合等离子体质谱法测量参与者的饮用水、头发和指甲的砷浓度。高血压的定义是收缩压（SBP）值≥140、舒张压（DBP）值≥90 mmHg。通过免疫测定法测量血清总亚硝酸盐浓度反映的血清NO水平。使用正式的因果中介分析来评估 NO 作为砷水平与高血压之间关联的中介。结果饮用水、头发和指甲中砷浓度的增加与收缩压和舒张压水平的增加有关。即使在暴露于相对低至中等水平（10-50μg/L）水中砷的参与者中，砷也呈剂量依赖性地增加高血压的几率[比值比（OR）和95％置信区间（CI）：2.87（95％） CI: 1.28, 6.44), 2.67 (95% CI: 1.10-50μg/L、50.01-150μg/L 和 >150μg/L 组分别为 27, 5.60) 和 5.04 (95% CI: 2.71, 9.35)]。因果中介分析显示，NO 对砷相关的收缩压、舒张压和高血压有显着的中介作用。结论 砷暴露量的增加与高血压发病率的增加有关。这种关联是通过降低血管一氧化氮生物利用度来介导的，这表明一氧化氮生物利用度受损是孟加拉人群砷诱发高血压的潜在机制。 https://doi.org/10.1289/EHP13018。