Endothelial dysfunction in the pulmonary artery induced by concentrated fine particulate matter exposure is associated with local but not systemic inflammation

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• 作者：Ana Paula Davel^a ; ^e ; ^{anadavel@unicamp.br} ; Miriam Lemos^b ; Luciana Manfré ; Pastro^b ; Sibelli Cosme Pedro^b ; Paulo Afonso de André ; ^c ; Cristina Hebeda^d ; Sandra Helena Farsky^d ; Paulo Hilá ; rio Saldiva^c ; Luciana Venturini Rossoni^e
• 关键词：Particulate matter ; Pulmonary artery ; Inflammatory cytokines ; Oxidative stress ; Nitric oxide
• 刊名：Toxicology
• 出版年：2012
• 期刊代码：47_0300483x
• 类别：pha
• 出版时间：16 May, 2012
• 卷：295
• 期：1-3
• 页码：39-46
• 文件大小：757 K

摘要

Clinical evidence has identified the pulmonary circulation as an important target of air pollution. It was previously demonstrated that in vitro exposure to fine particulate matter (aerodynamic diameter 鈮?.5 渭m, PM_2.5) induces endothelial dysfunction in isolated pulmonary arteries. We aimed to investigate the effects of in vivo exposure to urban concentrated PM_2.5 on rat pulmonary artery reactivity and the mechanisms involved. For this, adult Wistar rats were exposed to 2 weeks of concentrated S茫o Paulo city air PM_2.5 at an accumulated daily dose of approximately 600 渭g/m³. Pulmonary arteries isolated from PM_2.5-exposed animals exhibited impaired endothelium-dependent relaxation to acetylcholine without significant changes in nitric oxide donor response compared to control rats. PM_2.5 caused vascular oxidative stress and enhanced protein expression of Cu/Zn- and Mn-superoxide dismutase in the pulmonary artery. Protein expression of endothelial nitric oxide synthase (eNOS) was reduced, while tumor necrosis factor (TNF)-伪 was enhanced by PM_2.5 inhalation in pulmonary artery. There was a significant positive correlation between eNOS expression and maximal relaxation response (E_max) to acetylcholine. A negative correlation was found between vascular TNF-伪 expression and E_max to acetylcholine. Plasma cytokine levels, blood cells count and coagulation parameters were similar between control and PM_2.5-exposed rats. The present findings showed that in vivo daily exposure to concentrated urban PM_2.5 could decrease endothelium-dependent relaxation and eNOS expression on pulmonary arteries associated with local high TNF-伪 level but not systemic pro-inflammatory factors. Taken together, the present results elucidate the mechanisms underlying the trigger of cardiopulmonary diseases induced by urban ambient levels of PM_2.5.