Nurkiewicz Timothy R, Porter Dale W, Barger Mark, Castranova Vincent, Boegehold Matthew A
Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, West Virginia 26506-9229, USA.
Environ Health Perspect. 2004 Sep;112(13):1299-306. doi: 10.1289/ehp.7001.
Acute exposure to airborne pollutants, such as solid particulate matter (PM), increases the risk of cardiovascular dysfunction, but the mechanisms by which PM evokes systemic effects remain to be identified. The purpose of this study was to determine if pulmonary exposure to a PM surrogate, such as residual oil fly ash (ROFA), affects endothelium-dependent dilation in the systemic microcirculation. Rats were intratracheally instilled with ROFA at 0.1, 0.25, 1 or 2 mg/rat 24 hr before experimental measurements. Rats intratracheally instilled with saline or titanium dioxide (0.25 mg/rat) served as vehicle or particle control groups, respectively. In vivo microscopy of the spinotrapezius muscle was used to study systemic arteriolar dilator responses to the Ca2+ ionophore A23187, administered by ejection via pressurized micropipette into the arteriolar lumen. We used analysis of bronchoalveolar lavage (BAL) samples to monitor identified pulmonary inflammation and damage. To determine if ROFA exposure affected arteriolar nitric oxide sensitivity, sodium nitroprusside was iontophoretically applied to arterioles of rats exposed to ROFA. In saline-treated rats, A23187 dilated arterioles up to 72 +/- 7% of maximum. In ROFA- and TiO2-exposed rats, A23187-induced dilation was significantly attenuated. BAL fluid analysis revealed measurable pulmonary inflammation and damage after exposure to 1 and 2 mg ROFA (but not TiO2 or < 1 mg ROFA), as evidenced by significantly higher polymorphonuclear leukocyte cell counts, enhanced BAL albumin levels, and increased lactate dehydrogenase activity in BAL fluid. The sensitivity of arteriolar smooth muscle to NO was similar in saline-treated and ROFA-exposed rats, suggesting that pulmonary exposure to ROFA affected endothelial rather than smooth muscle function. A significant increase in venular leukocyte adhesion and rolling was observed in ROFA-exposed rats, suggesting local inflammation at the systemic microvascular level. These results indicate that pulmonary PM exposure impairs systemic endothelium-dependent arteriolar dilation. Moreover, because rats exposed to < 1 mg ROFA or TiO2 did not exhibit BAL signs of pulmonary damage or inflammation, it appears that PM exposure can impair systemic microvascular function independently of detectable pulmonary inflammation.
急性暴露于空气传播污染物，如固体颗粒物（PM），会增加心血管功能障碍的风险，但PM引发全身效应的机制仍有待确定。本研究的目的是确定肺部暴露于PM替代物，如残留油飞灰（ROFA），是否会影响体循环微循环中内皮依赖性舒张。在实验测量前24小时，给大鼠气管内滴注0.1、0.25、1或2mg/只的ROFA。气管内滴注生理盐水或二氧化钛（0.25mg/只）的大鼠分别作为载体或颗粒对照组。使用斜方肌的体内显微镜来研究全身小动脉对Ca2+离子载体A23187的舒张反应，通过加压微量移液器将其喷射到小动脉腔内给药。我们使用支气管肺泡灌洗（BAL）样本分析来监测已确定的肺部炎症和损伤。为了确定ROFA暴露是否影响小动脉对一氧化氮的敏感性，将硝普钠通过离子电渗法应用于暴露于ROFA的大鼠的小动脉。在生理盐水处理的大鼠中，A23187使小动脉舒张至最大舒张度的72±7%。在暴露于ROFA和TiO2的大鼠中，A23187诱导的舒张显著减弱。BAL液分析显示，暴露于1和2mg ROFA（但不是TiO2或<1mg ROFA）后可检测到肺部炎症和损伤，表现为多形核白细胞计数显著升高、BAL白蛋白水平升高以及BAL液中乳酸脱氢酶活性增加。生理盐水处理的大鼠和暴露于ROFA的大鼠中小动脉平滑肌对NO的敏感性相似，这表明肺部暴露于ROFA影响的是内皮功能而非平滑肌功能。在暴露于ROFA的大鼠中观察到小静脉白细胞黏附和滚动显著增加，表明在体循环微血管水平存在局部炎症。这些结果表明，肺部暴露于PM会损害全身内皮依赖性小动脉舒张。此外，由于暴露于<1mg ROFA或TiO2的大鼠未表现出肺部损伤或炎症的BAL迹象，似乎PM暴露可独立于可检测到的肺部炎症损害体循环微血管功能。
