Sack Cora S, Jansen Karen L, Cosselman Kristen E, Trenga Carol A, Stapleton Pat L, Allen Jason, Peretz Alon, Olives Casey, Kaufman Joel D
1 Department of Environmental and Occupational Health, University of Washington, Seattle, Washington; and.
2 Rabin Medical Center, Tel Aviv University, Tel Aviv, Israel.
Am J Respir Crit Care Med. 2016 May 1;193(9):1000-7. doi: 10.1164/rccm.201506-1247OC.
Diesel exhaust inhalation, which is the model traffic-related air pollutant exposure, is associated with vascular dysfunction.
To determine whether healthy subjects exposed to diesel exhaust exhibit acute vasoconstriction and whether this effect could be modified by the use of antioxidants or by common variants in the angiotensin II type 1 receptor (AGTR1) and other candidate genes.
In a genotype-stratified, double-blind, four-way crossover study, 21 healthy adult subjects were exposed at rest in a randomized, balanced order to diesel exhaust (200 μg/m(3) particulate matter with an aerodynamic diameter ≤ 2.5 μm [PM2.5]) and filtered air, and to pretreatment with antioxidants (N-acetylcysteine and ascorbate) and placebo. Before and after each exposure, brachial artery diameter (BAd) was assessed using ultrasound. Changes in BAd were compared across pretreatment and exposure sessions. Gene-exposure interactions were evaluated in the AGTR1 A1166C polymorphism, on which recruitment was stratified, and other candidate genes, including TRPV1 and GSTM1.
Compared with filtered air, exposure to diesel exhaust resulted in a significant reduction in BAd (mean, -0.09 mm, 95% confidence interval [CI], -0.01 to -0.17; P = 0.03). Pretreatment with antioxidants augmented diesel exhaust-related vasoconstriction with a mean change in BAd of -0.18 mm (95% CI, -0.28 to -0.07 mm; P = 0.001). Diesel exhaust-related vasoconstriction was primarily observed in the variant alleles of AGTR1 and TRPV1. No association was found between diesel exhaust inhalation and flow-mediated dilation.
We confirmed that short-term exposure to diesel exhaust in healthy subjects is associated with acute vasoconstriction in a conductance artery and found suggestive evidence of involvement of nociception and renin-angiotensin systems in this effect. Pretreatment with an antioxidant regimen increased vasoconstriction.
吸入柴油废气是与交通相关的典型空气污染物暴露方式，与血管功能障碍有关。
确定暴露于柴油废气的健康受试者是否会出现急性血管收缩，以及这种效应是否可以通过使用抗氧化剂或通过血管紧张素II 1型受体（AGTR1）及其他候选基因的常见变异来改变。
在一项基因分型分层、双盲、四向交叉研究中，21名健康成年受试者在静息状态下以随机、平衡的顺序暴露于柴油废气（200μg/m³空气动力学直径≤2.5μm的颗粒物[PM2.5]）和过滤空气中，并预先使用抗氧化剂（N-乙酰半胱氨酸和抗坏血酸盐）和安慰剂进行处理。每次暴露前后，使用超声评估肱动脉直径（BAd）。比较预处理和暴露阶段BAd的变化。在AGTR1 A1166C多态性（招募时进行了分层）以及其他候选基因（包括TRPV1和GSTM1）中评估基因-暴露相互作用。
与过滤空气相比，暴露于柴油废气导致BAd显著减小（平均值为-0.09mm，95%置信区间[CI]为-0.01至-0.17；P = 0.03）。用抗氧化剂预处理增强了与柴油废气相关的血管收缩，BAd的平均变化为-0.18mm（95%CI为-0.28至-0.07mm；P = 0.001）。与柴油废气相关的血管收缩主要在AGTR1和TRPV1的变异等位基因中观察到。吸入柴油废气与血流介导的血管舒张之间未发现关联。
我们证实，健康受试者短期暴露于柴油废气与传导动脉的急性血管收缩有关，并发现了伤害感受和肾素-血管紧张素系统参与此效应的提示性证据。抗氧化剂方案预处理增加了血管收缩。
