Cardiac oxidative stress and electrophysiological changes in rats exposed to concentrated ambient particles are mediated by TRP-dependent pulmonary reflexes
Cardiac oxidative stress and electrophysiological changes in rats exposed to concentrated ambient particles are mediated by TRP-dependent pulmonary reflexes
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DOI：
10.1093/toxsci/kfn005
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发表时间：
2008-04-01
影响因子：
3.8
通讯作者：
Gonzalez-Flecha, Beatriz
中科院分区：
文献类型：
--
作者：
Ghelfi, Elisa;Ramos-Rhoden, Claudia;Gonzalez-Flecha, Beatriz
先前的研究表明，通过刺激肺神经末梢，环境颗粒调节心脏的自主神经张力，导致心脏氧化应激和功能障碍。在本文中，我们在吸入暴露的大鼠模型中研究了阻断香草酸受体 1（瞬时受体电位香草酸受体 1 [TRPV1]）对浓缩环境颗粒 (CAP) 诱导的心脏氧化应激和功能障碍的影响。 Capsazepine (CPZ) 是一种 TRPV1 的选择性拮抗剂，在接触 CAP 之前立即通过腹腔注射或气雾剂给药。使用哈佛环境颗粒浓缩器（平均 PM2.5 质量浓度：218 +/- 23 mu g/m(3)）将对照和 CPZ 治疗的大鼠暴露于过滤空气或 CAP 气溶胶中 5 小时。在暴露结束时，我们测量了心脏氧化应激（原位化学发光[CL]）、脂质过氧化（硫代巴比妥酸反应物质[TBARS]）和组织水肿。在整个暴露过程中监测心脏功能。 CPZ（腹腔注射或气雾剂）可降低 CAP 诱导的 CL、脂质 TBARS 和心脏水肿，表明全身或局部阻断 TRP 受体可降低心脏 CL。 CAP 暴露导致心率显着降低（CAP 350 +/- 32 bpm，对照：370 +/- 29）以及 QT、RT、Pdur 和 Tpe 间期长度显着降低。这些变化在接触后立即可见，并且在吸入 CAP 的整个 5 小时内保持不变。 CPZ 可预防心律和心电图形态的变化。这些数据表明，目前暴露于 CAP 的大鼠的异常改变了动作电位，导致传导速度和心室复极的变化，并且触发肺中 TRPV1 介导的自主反射对于观察到的心律变化至关重要。
Previous studies suggest that, through the stimulation of pulmonary nervous endings, ambient particles modulate the autonomic tone on the heart leading to cardiac oxidant stress and dysfunction. In this paper we investigated the effect of blockade of vanilloid receptor 1 (Transient Receptor Potential Vanilloid Receptor 1 [TRPV1]) on concentrated ambient particles (CAPs)-induced cardiac oxidative stress and dysfunction in a rat model of inhalation exposure. Capsazepine (CPZ), a selective antagonist of TRPV1, was given ip or as an aerosol immediately before exposure to CAPs. Control and CPZ-treated rats were exposed to filtered air or CAPs aerosols for 5 h using the Harvard Ambient Particle Concentrator (mean PM2.5 mass concentration: 218 +/- 23 mu g/m(3)). At the end of the exposure we measured cardiac oxidative stress (in situ chemiluminescence [CL]), lipid peroxidation (thiobarbituric acid reactive substances [TBARS]), and tissue edema. Cardiac function was monitored throughout the exposure. CPZ (ip or aerosol) decreased CAPs-induced CL, lipid TBARS, and edema in the heart, indicating that blocking TRP receptors, systemically or locally, decreases heart CL. CAPs exposure led to significant decreases in heart rate (CAPs 350 +/- 32 bpm, control: 370 +/- 29), and in the length of the QT, RT, Pdur and Tpe intervals. These changes were observable immediately upon exposure and were maintained throughout the 5 h of CAPs inhalation. Changes in cardiac rhythm and electrocardiogram morphology were prevented by CPZ. These data suggest that current abnormalities in CAPs-exposed rats alter the action potentials leading to changes in conduction velocity and ventricular repolarization, and that triggering of TRPV1-mediated autonomic reflexes in the lung is essential for the observed changes in cardiac rhythms.