Department of Physiology and Biophysics, ICB, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
PLoS One. 2013 Sep 9;8(9):e73562. doi: 10.1371/journal.pone.0073562. eCollection 2013.
Paraquat is a toxic herbicide that may induce acute lung injury, circulatory failure and death. The present work aimed at investigating whether there is systemic inflammation and vascular dysfunction after paraquat exposure and whether these parameters were related. There was neutrophilia and accumulation of neutrophils in lung and bronchoalveolar lavage of animals given paraquat. This was associated with an increase in serum levels of TNF-α. In rats given paraquat, the relaxant response of aortic rings to acetylcholine was not modified but the contractile response to phenylephrine was greatly reduced. Endothelium removal or treatment with non-selective (L-NAME) or selective (L-NIL) inhibitors of inducible nitric oxide synthase (iNOS) restored contraction of aortas. There was greater production of nitric oxide (NO), which was restored to basal level by L-NIL, and greater expression of iNOS in endothelial cells, as seen by Western blot analyses and confocal microscopy. Blockade of TNF-α reduced pulmonary and systemic inflammation and vascular dysfunction. Together, our results clearly show that paraquat causes pulmonary and systemic inflammation, and vascular dysfunction in rats. Vascular dysfunction is TNF-α dependent, associated with enhanced expression of iNOS in aortic endothelial cells and greater NO production, which accounts for the decreased responsiveness of aortas to vasoconstrictors. Blockers of TNF-α may be useful in patients with paraquat poisoning.
百草枯是一种有毒的除草剂，可能会导致急性肺损伤、循环衰竭和死亡。本研究旨在探讨百草枯暴露后是否存在全身炎症和血管功能障碍，以及这些参数是否相关。给予百草枯的动物的肺和支气管肺泡灌洗液中出现中性粒细胞增多和中性粒细胞积聚，同时伴有 TNF-α 血清水平升高。在给予百草枯的大鼠中，主动脉环对乙酰胆碱的舒张反应没有改变，但对苯肾上腺素的收缩反应大大降低。内皮细胞去除或使用非选择性（L-NAME）或选择性（L-NIL）诱导型一氧化氮合酶（iNOS）抑制剂处理可恢复主动脉的收缩。产生的一氧化氮（NO）增加，L-NIL 将其恢复到基础水平，并且通过 Western blot 分析和共聚焦显微镜观察到内皮细胞中 iNOS 的表达增加。TNF-α 阻断可减轻肺和全身炎症以及血管功能障碍。综上所述，我们的研究结果清楚地表明，百草枯会导致大鼠肺部和全身炎症以及血管功能障碍。血管功能障碍依赖于 TNF-α，与主动脉内皮细胞中 iNOS 的表达增强和 NO 产生增加有关，这导致了对血管收缩剂反应性降低。TNF-α 阻断剂可能对百草枯中毒患者有用。
