TRPA1 and sympathetic activation contribute to increased risk of triggered cardiac arrhythmias in hypertensive rats exposed to diesel exhaust.
TRPA1 and sympathetic activation contribute to increased risk of triggered cardiac arrhythmias in hypertensive rats exposed to diesel exhaust.
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DOI：
10.1289/ehp.1003200
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发表时间：
2011-07
影响因子：
10.4
通讯作者：
Farraj AK
中科院分区：
文献类型：
--
作者：
Hazari MS;Haykal-Coates N;Winsett DW;Krantz QT;King C;Costa DL;Farraj AK
Background: Diesel exhaust (DE), which is emitted from on- and off-road sources, is a complex mixture of toxic gaseous and particulate components that leads to triggered adverse cardiovascular effects such as arrhythmias. Objective: We hypothesized that increased risk of triggered arrhythmias 1 day after DE exposure is mediated by airway sensory nerves bearing transient receptor potential (TRP) channels [e.g., transient receptor potential cation channel, member A1 (TRPA1)] that, when activated by noxious chemicals, can cause a centrally mediated autonomic imbalance and heightened risk of arrhythmia. Methods: Spontaneously hypertensive rats implanted with radiotelemeters were whole-body exposed to either 500 μg/m3 (high) or 150 μg/m3 (low) whole DE (wDE) or filtered DE (fDE), or to filtered air (controls), for 4 hr. Arrhythmogenesis was assessed 24 hr later by continuous intravenous infusion of aconitine, an arrhythmogenic drug, while heart rate (HR) and electrocardiogram (ECG) were monitored. Results: Rats exposed to wDE or fDE had slightly higher HRs and increased low-frequency:high-frequency ratios (sympathetic modulation) than did controls; ECG showed prolonged ventricular depolarization and shortened repolarization periods. Rats exposed to wDE developed arrhythmia at lower doses of aconitine than did controls; the dose was even lower in rats exposed to fDE. Pretreatment of low wDE–exposed rats with a TRPA1 antagonist or sympathetic blockade prevented the heightened sensitivity to arrhythmia. Conclusions: These findings suggest that a single exposure to DE increases the sensitivity of the heart to triggered arrhythmias. The gaseous components appear to play an important role in the proarrhythmic response, which may be mediated by activation of TRPA1, and subsequent sympathetic modulation. As such, toxic inhalants may partly exhibit their toxicity by lowering the threshold for secondary triggers, complicating assessment of their risk.
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影响因子：
4.9
作者：
Rich, D. Q.;Kim, M. H.;Dockery, D. W.
通讯作者：
Dockery, D. W.
吸入高浓度环境微粒会产生一致的肺部和全身反应： 所用大鼠品系和理化特性的作用
影响因子：
10.4
作者：
Kodavanti, UP;Schladweiler, MC;Costa, DL
通讯作者：
Costa, DL
影响因子：
3.8
作者：
Ghelfi, Elisa;Ramos-Rhoden, Claudia;Gonzalez-Flecha, Beatriz
通讯作者：
Gonzalez-Flecha, Beatriz
影响因子：
8.3
作者：
Peretz, Alon;Kaufman, Joel D.;Sullivan, Jeffrey H.
通讯作者：
Sullivan, Jeffrey H.
DOI：
10.1152/physiol.00026.2008
发表时间：
2008-12
期刊：
Physiology (Bethesda, Md.)
影响因子：
--
作者：
Bessac BF;Jordt SE
通讯作者：
Jordt SE