Avignon University, France.
Cardiovasc Toxicol. 2011 Dec;11(4):334-40. doi: 10.1007/s12012-011-9125-z.
Chronic exposure to simulated urban CO pollution is reported to be associated with cardiac dysfunction. Despite the potential implication of myocardial perfusion alteration in the pathophysiology of CO pollution, the underlying mechanisms remain today still unknown. Therefore, the aim of this work was to evaluate the effects of prolonged exposure to simulated urban CO pollution on the regulation of myocardial perfusion. Cardiac hemodynamics and myocardial perfusion were assessed under basal conditions and during the infusion of a β-Adrenergic agonist. The effects of CO exposure on capillary density, coronary endothelium-dependent vasodilatation, eNOS expression and eNOS uncoupling were also evaluated. Our main results were that prolonged CO exposure was associated with a blunted myocardial perfusion response to a physiological stress responsible for an altered contractile reserve. The impairment of myocardial perfusion reserve was not accounted for a reduced capillary density but rather by an alteration in coronary endothelium-dependent vasorelaxation (-45% of maximal relaxation to ACh). In addition, though chronic CO exposure did not change eNOS expression, it significantly increased eNOS uncoupling. Therefore, the present work underlines the fact that chronic CO exposure, at levels found in urban air pollution, is associated with reduced myocardial perfusion reserve. This phenomenon is explained at the coronary-vessel level by deleterious effects of CO exposure on the endothelium NO-dependent vasorelaxation via eNOS uncoupling.
慢性暴露于模拟城市 CO 污染被报道与心脏功能障碍有关。尽管心肌灌注改变在 CO 污染的病理生理学中具有潜在的意义，但这些机制至今仍不清楚。因此，本研究的目的是评估长期暴露于模拟城市 CO 污染对心肌灌注调节的影响。在基础条件下和β-肾上腺素能激动剂输注期间评估心脏血液动力学和心肌灌注。还评估了 CO 暴露对毛细血管密度、冠状动脉内皮依赖性血管舒张、eNOS 表达和 eNOS 解偶联的影响。我们的主要结果是，长期 CO 暴露与对生理应激的心肌灌注反应迟钝有关，这种应激会导致收缩储备改变。心肌灌注储备的损害不是由于毛细血管密度降低，而是由于冠状动脉内皮依赖性血管舒张的改变（ACh 最大松弛度降低 45%）。此外，尽管慢性 CO 暴露不会改变 eNOS 表达，但它显著增加了 eNOS 解偶联。因此，本研究强调了这样一个事实，即在城市空气污染中发现的 CO 慢性暴露与心肌灌注储备减少有关。这种现象在冠状动脉水平上可以通过 CO 暴露通过 eNOS 解偶联对内皮细胞 NO 依赖性血管舒张的有害影响来解释。
