Direct impairment of vascular function by diesel exhaust particulate through reduced bioavailability of endothelium-derived nitric oxide induced by superoxide free radicals.
Direct impairment of vascular function by diesel exhaust particulate through reduced bioavailability of endothelium-derived nitric oxide induced by superoxide free radicals.
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DOI：
10.1289/ehp.0800235
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发表时间：
2009-04
影响因子：
10.4
通讯作者：
Newby DE
中科院分区：
文献类型：
--
作者：
Miller MR;Borthwick SJ;Shaw CA;McLean SG;McClure D;Mills NL;Duffin R;Donaldson K;Megson IL;Hadoke PW;Newby DE
柴油机排气颗粒物（DEP）是空气污染对心血管不良影响的关键仲裁者。我们评估了DEP对血管功能、一氧化氮（NO）利用率和以氧为中心的自由基产生的体外影响。我们使用肌造影术评估DEP（10-100 μg/mL）在离体大鼠主动脉环中的直接血管效应。我们研究了NO清除和氧为中心的自由基的产生，分别使用NO电极和电子顺磁共振（EPR）与Tempone-H（1-羟基-2，2，6，6-四甲基-4-氧代-哌啶）自旋陷阱。乙酰胆碱诱导的舒张被DEP减弱（最大舒张从91 ± 4%降低到100 μg/mL DEP的49 ± 6%; p < 0.001），但被超氧化物歧化酶恢复（SOD;最大舒张，73 ± 6%; p < 0.001）。DEP对NO供体药物的舒张作用有一定的抑制作用，这种作用可被SOD逆转（p < 0.01）。在10 μg/mL时，DEP不影响维拉帕米诱导的舒张（p = 0.73），但在100 μg/mL时，DEP通过独立于SOD的机制抑制舒张（p < 0.001）。DEP降低了2-（N，N-二乙基氨基）-二氮烯-2-氧化物（DEA/NO; 10 μM）产生的NO浓度（100 μg/mL;从5.2 ± 0.4 μM降至3.3 ± 0.4 μM; p = 0.002）。DEP（10 μg/mL; EPR光谱增加9倍; p = 0.004）以SOD（p = 0.015）可减弱的方式增加自由基生成。DEP通过产生以氧为中心的自由基引起氧化应激，从而降低内皮源性NO的生物利用度，而无需事先与肺或血管组织相互作用。这些发现为颗粒空气污染对心血管的不良影响提供了一种机制。
Diesel exhaust particulate (DEP) is a key arbiter of the adverse cardiovascular effects of air pollution. We assessed the in vitro effects of DEP on vascular function, nitric oxide (NO) availability, and the generation of oxygen-centered free radicals. We assessed the direct vascular effects of DEP (10–100 μg/mL) in isolated rat aortic rings using myography. We investigated NO scavenging and oxygen-centered free radical generation using an NO electrode and electron paramagnetic resonance (EPR) with the Tempone-H (1-hydroxyl-2,2,6,6-tetramethyl-4-oxo-piperidine) spin trap, respectively. Acetylcholine-induced relaxation was attenuated by DEP (maximum relaxation reduced from 91 ± 4% to 49 ± 6% with 100 μg/mL DEP; p < 0.001) but was restored by superoxide dismutase (SOD; maximum relaxation, 73 ± 6%; p < 0.001). DEP caused a modest inhibition of relaxation to NO donor drugs, an effect that could be reversed by SOD (p < 0.01). At 10 μg/mL, DEP did not affect verapamil-induced relaxation (p = 0.73), but at 100 μg/mL DEP inhibited relaxation (p < 0.001) by a mechanism independent of SOD. NO concentrations generated by 2-(N,N-diethylamino)-diazenolate-2-oxide (DEA/NO; 10 μM) were reduced by DEP (100 μg/mL; from 5.2 ± 0.4 to 3.3 ± 0.4 μM; p = 0.002). Free radical generation was increased by DEP (10 μg/mL; 9-fold increase in EPR spectra; p = 0.004) in a manner that could be attenuated by SOD (p = 0.015). DEP caused oxidative stress through the generation of oxygen-centered free radicals that reduced the bioavailability of endothelium-derived NO without prior interaction with the lung or vascular tissue. These findings provide a mechanism for the adverse cardiovascular effects of particulate air pollution.
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影响因子：
2.1
作者：
Dvonch, JT;Brook, RD;Harkema, JR
通讯作者：
Harkema, JR
影响因子：
2.8
作者：
Knaapen, AM;den Hartog, GJ;Borm, PJA
通讯作者：
Borm, PJA
影响因子：
3.8
作者：
Bagate, K;Meiring, JJ;Borm, PJA
通讯作者：
Borm, PJA
影响因子：
4.5
作者：
Aam, Berit Bjugan;Fonnum, F.
通讯作者：
Fonnum, F.
影响因子：
6.1
作者：
Chauhan, V;Breznan, D;Vincent, R
通讯作者：
Vincent, R