Department of Physiology, Faculty of Medicine and Health Sciences, United Arab Emirates University, PO Box 17666, Al Ain, United Arab Emirates.
Toxicology. 2011 Jul 11;285(1-2):39-45. doi: 10.1016/j.tox.2011.03.018. Epub 2011 Apr 8.
Several epidemiological studies have shown that acute exposure to particulate air pollution is associated with increases in cardiovascular morbidity and mortality, and that these effects are especially exacerbated among individuals with pre-existing compromised cardiovascular function such as hypertension. This study was undertaken to determine the cardiovascular effect of diesel exhaust on TO mice made hypertensive by implanting osmotic minipump infusing angiotensin II or vehicle (control). On day 13, the animals were intratracheally instilled with either DEP (15 μg/mouse) or saline. 24 h later, pulmonary exposure to DEP had significantly decreased the systolic blood pressure (SBP) in hypertensive (HT) mice (P<0.01), but not in normotensive (NT) mice. The number of leukocytes and red blood cells, and the plasma interleukin 6 concentration in plasma, however, were not affected in any of the animals. The PaO₂ was decreased, and PaCO₂ increased in DEP-treated HT mice compared to NT mice treated with DEP (P<0.05). The number of circulating platelets was significantly increased in DEP-treated HT versus saline-treated HT and DEP-treated NT mice. Moreover, in NT mice, DEP exposure induced a prothrombotic effect in pial arterioles compared with saline-treated NT mice (P<0.05). Interestingly, in DEP-treated HT mice, the prothrombotic events were significantly aggravated compared with saline-treated HT and DEP-treated NT mice. The direct addition of DEP (0.1-1 μg/ml) to untreated mouse blood significantly induced in vitro platelet aggregation in a dose-dependent fashion, and these effects were more pronounced in blood of HT mice. In vitro exposure to DEP (0.25-1 μg/ml) led to activated intravascular coagulation, an effect that was confirmed by a shortening of both the activated partial thromboplastin time (aPTT) and the prothrombin time (PT). The effect of DEP on aPTT was potentiated in the plasma of HT mice. It can be concluded that the thrombotic events caused by DEP are exacerbated by hypertension in mice. Our findings, therefore, provide a possible plausible explanation for the cardiovascular morbidity and mortality accompanying urban air pollution.
几项流行病学研究表明，急性暴露于颗粒物空气污染与心血管发病率和死亡率的增加有关，而这些影响在已有心血管功能受损的个体中尤为严重，如高血压。本研究旨在确定柴油机排气对植入血管紧张素 II 或载体（对照）渗透微型泵的 TO 高血压小鼠的心血管影响。第 13 天，动物经气管内滴注 DEP（15 μg/只）或生理盐水。24 小时后，DEP 肺部暴露显著降低了高血压（HT）小鼠的收缩压（SBP）（P<0.01），但对正常血压（NT）小鼠没有影响。然而，在任何动物中，白细胞和红细胞的数量以及血浆中的白细胞介素 6 浓度都没有受到影响。与 DEP 处理的 NT 小鼠相比，DEP 处理的 HT 小鼠的 PaO₂降低，PaCO₂升高（P<0.05）。与生理盐水处理的 HT 和 DEP 处理的 NT 小鼠相比，DEP 处理的 HT 小鼠的循环血小板数量显著增加。此外，在 NT 小鼠中，与生理盐水处理的 NT 小鼠相比，DEP 暴露诱导软脑膜小动脉形成促血栓形成效应（P<0.05）。有趣的是，在 DEP 处理的 HT 小鼠中，与生理盐水处理的 HT 和 DEP 处理的 NT 小鼠相比，促血栓形成事件明显加重。DEP（0.1-1 μg/ml）直接加入未经处理的小鼠血液中，以剂量依赖性方式显著诱导体外血小板聚集，而 HT 小鼠的血液中这些效应更为明显。体外暴露于 DEP（0.25-1 μg/ml）导致血管内凝血激活，这一效应通过激活部分凝血活酶时间（aPTT）和凝血酶原时间（PT）的缩短得到证实。DEP 对 aPTT 的作用在 HT 小鼠的血浆中得到增强。可以得出结论，DEP 引起的血栓形成事件在高血压小鼠中加剧。因此，我们的研究结果为城市空气污染伴随的心血管发病率和死亡率提供了一个可能的合理解释。
