Nanoparticle inhalation impairs coronary microvascular reactivity via a local reactive oxygen species-dependent mechanism.
Nanoparticle inhalation impairs coronary microvascular reactivity via a local reactive oxygen species-dependent mechanism.
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DOI：
10.1007/s12012-009-9060-4
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发表时间：
2010-03
影响因子：
3.2
通讯作者：
Nurkiewicz, T. R.
中科院分区：
文献类型：
--
作者：
LeBlanc, A. J.;Moseley, A. M.;Chen, B. T.;Frazer, D.;Castranova, V.;Nurkiewicz, T. R.
关键词：
我们已经表明，纳米颗粒吸入损害冠状动脉内皮依赖性血管舒张。目前尚不清楚局部活性氧（ROS）是否有助于这种效应。大鼠通过吸入暴露于TiO 2纳米颗粒，以产生10 µg的肺部沉积。从左前降支动脉分布中分离冠状小动脉，并评估对乙酰胆碱、花生四烯酸和U46619的反应。通过与NG-单甲基-L-精氨酸（L-NMMA）和吲哚美辛的竞争性抑制来评估一氧化氮合酶和前列腺素的贡献。通过二氢乙锭（DHE）荧光定量微血管壁ROS。暴露于纳米二氧化钛的大鼠冠状动脉表现出衰减血管扩张反应乙酰胆碱，这与DHE荧光增加45%。与2，2，6，6-四甲基哌啶-N-氧自由基和过氧化氢酶共孵育可改善暴露于纳米颗粒的大鼠ACh诱导的血管舒张损伤。无论是L-NMMA或吲哚美辛孵育显着衰减乙酰胆碱诱导的血管舒张假对照大鼠，但在大鼠暴露于纳米二氧化钛没有影响。花生四烯酸诱导暴露于纳米二氧化钛的大鼠冠状动脉血管收缩，但从假手术对照组大鼠扩张微动脉。这些结果表明，纳米颗粒暴露显着损害冠状动脉内皮依赖性血管反应性，这可能是由于在很大程度上增加微血管活性氧。此外，前列腺素形成的改变也可能导致这种功能障碍。冠状动脉微血管功能的这种紊乱可能导致与暴露于该尺寸范围内的颗粒相关的心脏事件。
We have shown that nanoparticle inhalation impairs endothelium-dependent vasodilation in coronary arterioles. It is unknown whether local reactive oxygen species (ROS) contribute to this effect. Rats were exposed to TiO2 nanoparticles via inhalation to produce a pulmonary deposition of 10 µg. Coronary arterioles were isolated from the left anterior descending artery distribution, and responses to acetylcholine, arachidonic acid, and U46619 were assessed. Contributions of nitric oxide synthase and prostaglandin were assessed via competitive inhibition with NG-Monomethyl-L-Arginine (L-NMMA) and indomethacin. Microvascular wall ROS were quantified via dihydroethidium (DHE) fluorescence. Coronary arterioles from rats exposed to nano-TiO2 exhibited an attenuated vasodilator response to ACh, and this coincided with a 45% increase in DHE fluorescence. Coincubation with 2,2,6,6-tetramethylpiperidine-N-oxyl and catalase ameliorated impairments in ACh-induced vasodilation from nanoparticle exposed rats. Incubation with either L-NMMA or indomethacin significantly attenuated Ach-induced vasodilation in sham-control rats, but had no effect in rats exposed to nano-TiO2. Arachidonic acid induced vasoconstriction in coronary arterioles from rats exposed to nano-TiO2, but dilated arterioles from sham-control rats. These results suggest that nanoparticle exposure significantly impairs endothelium-dependent vasoreactivity in coronary arterioles, and this may be due in large part to increases in microvascular ROS. Furthermore, altered prostanoid formation may also contribute to this dysfunction. Such disturbances in coronary microvascular function may contribute to the cardiac events associated with exposure to particles in this size range.
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DOI：
10.1161/atvbaha.108.176107
发表时间：
2009-04
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Lund AK;Lucero J;Lucas S;Madden MC;McDonald JD;Seagrave JC;Knuckles TL;Campen MJ
通讯作者：
Campen MJ
DOI：
10.1080/15287390903232467
发表时间：
2009
期刊：
Journal of toxicology and environmental health. Part A
影响因子：
--
作者：
LeBlanc AJ;Cumpston JL;Chen BT;Frazer D;Castranova V;Nurkiewicz TR
通讯作者：
Nurkiewicz TR
影响因子：
--
作者：
CHILIAN, WM;EASTHAM, CL;MARCUS, ML
通讯作者：
MARCUS, ML
影响因子：
10.4
作者：
Nurkiewicz, Timothy R;Porter, Dale W;Barger, Mark;Millecchia, Lyndell;Rao, K Murali K;Marvar, Paul J;Hubbs, Ann F;Castranova, Vincent;Boegehold, Matthew A
通讯作者：
Boegehold, Matthew A
影响因子：
10.4
作者：
Miller MR;Borthwick SJ;Shaw CA;McLean SG;McClure D;Mills NL;Duffin R;Donaldson K;Megson IL;Hadoke PW;Newby DE
通讯作者：
Newby DE