Dvonch J Timothy, Brook Robert D, Keeler Gerald J, Rajagopalan Sanjay, D'Alecy Louis G, Marsik Frank J, Morishita Masako, Yip Fuyuen Y, Brook Jeffrey R, Timm Edward J, Wagner James G, Harkema Jack R
Department of Environmental Health Sciences, University of Michigan, Ann Arbor, 48109-2029, USA. dvonch@umichedu
Inhal Toxicol. 2004 Jun;16(6-7):473-80. doi: 10.1080/08958370490439678.
The health effects of ambient fine particulate matter (PM(2.5)) and its potential impact on vascular endothelial function have not been thoroughly investigated. As endothelial dysfunction plays an important role in the pathogenesis of atherosclerosis and its complications, we examined the effects of concentrated fine ambient particles (CAPs) on the plasma level of asymmetric dimethylarginine (ADMA) in a pilot study. ADMA is a circulating endogenous inhibitor of nitric oxide synthase (NOS) that is associated with impaired vascular function and increased risk for cardiovascular events. A mobile air research laboratory (AirCARE 1) was used to provide "real-world" CAPs exposures for this study conducted in Detroit, MI. Fourteen Brown Norway rats were exposed to filtered air (FA) (n = 7) or CAPs (0.1-2.5 microm) (n = 7) for 3 consecutive days (8 h/day) in July 2002. Rats were exposed during these periods to average particle mass concentrations of 354 microg/m(3). Rat plasma samples were collected 24 h postexposure. Plasma concentrations of ADMA were significantly elevated in rats exposed to CAPs versus those exposed to FA (mean +/- standard deviation = 1.49 +/- 0.18 vs. 1.29 +/- 0.26 microM, p =.05 by one-tailed t-test). Analyses of meteorological data and CAPs trace element composition suggest that local particle emission sources contributed largely to overall mass of CAPs. Results of this pilot study suggest that exposure to PM(2.5) at high concentrations may trigger an acute increase in circulating ADMA level. This finding has implications for the regulation of vasomotor tone by particulate pollutants and the propensity for adverse cardiovascular events.
环境细颗粒物(PM2.5)对健康的影响及其对血管内皮功能的潜在影响尚未得到充分研究。由于内皮功能障碍在动脉粥样硬化及其并发症的发病机制中起重要作用,我们在一项初步研究中检测了浓缩环境细颗粒物(CAPs)对不对称二甲基精氨酸(ADMA)血浆水平的影响。ADMA是一氧化氮合酶(NOS)的循环内源性抑制剂,与血管功能受损和心血管事件风险增加有关。本研究在密歇根州底特律市进行,使用了一个移动空气研究实验室(AirCARE 1)来提供“真实世界”的CAPs暴露环境。2002年7月,14只棕色挪威大鼠连续3天(每天8小时)暴露于过滤空气(FA)(n = 7)或CAPs(0.1 - 2.5微米)(n = 7)中。在这些时间段内,大鼠暴露于平均颗粒物质量浓度为354微克/立方米的环境中。暴露24小时后采集大鼠血浆样本。与暴露于FA的大鼠相比,暴露于CAPs的大鼠血浆ADMA浓度显著升高(平均值±标准差 = 1.49±0.18对1.29±0.26微摩尔,单尾t检验p = 0.05)。气象数据和CAPs微量元素组成分析表明,当地颗粒物排放源在很大程度上构成了CAPs的总体质量。这项初步研究结果表明,高浓度暴露于PM2.5可能会引发循环ADMA水平的急性升高。这一发现对于颗粒物污染物对血管舒缩张力的调节以及不良心血管事件的易感性具有重要意义。