Department of Physiology and Biophysics, ICB, Federal University of Minas Gerais, Av. Antônio Carlos, 6627 Pampulha 31270-901, Belo Horizonte, MG, Brazil.
Toxicol In Vitro. 2010 Apr;24(3):1019-25. doi: 10.1016/j.tiv.2009.12.003. Epub 2009 Dec 11.
Paraquat is a toxic herbicide that induces severe acute lung injury (ALI) and pulmonary hypertension in humans. Although vascular disorders are present and contribute to increased mortality in ALI patients, there is little data available on vascular responsiveness after toxic exposure to paraquat. We aimed to evaluate the vascular response of isolated pulmonary arteries from rats treated with a dose of paraquat that induces ALI. Paraquat treatment did not modify the relaxant response of pulmonary artery to acetylcholine, but greatly reduced phenylephrine-induced contraction. Removal of the endothelium, inhibition of nitric oxide synthase (NOS) with L-NAME or selective inhibition of inducible NOS (iNOS) with L-NIL, restored contraction of vessels from paraquat poisoned rats to the same level as those not exposed to paraquat. The basal production of NO and expression of iNOS were increased in endothelium-intact but not in endothelium-denuded vessels from paraquat-poisoned rats. Expression of endothelial NOS was not modified. Our findings suggest that paraquat poisoning increases endothelial iNOS expression and basal NO production decreasing responsiveness of pulmonary artery to vasoconstrictors. Thus, our results do not support the hypothesis that pulmonary hypertension in paraquat-induced ALI is mediated by a reduction in endothelial NO production or increased contractility of pulmonary artery.
百草枯是一种有毒的除草剂，会导致人类出现严重的急性肺损伤（ALI）和肺动脉高压。尽管血管紊乱存在，并导致 ALI 患者死亡率增加，但关于百草枯中毒后血管反应性的数据很少。我们旨在评估用诱导 ALI 的百草枯剂量处理的大鼠离体肺血管的血管反应。百草枯处理不会改变肺血管对乙酰胆碱的舒张反应，但大大降低了苯肾上腺素引起的收缩。去除内皮细胞、用 L-NAME 抑制一氧化氮合酶（NOS）或用 L-NIL 选择性抑制诱导型 NOS（iNOS），可使百草枯中毒大鼠的血管收缩恢复到未暴露于百草枯的血管水平。内皮完整的但内皮去神经的百草枯中毒大鼠的血管中，NO 的基础产生和 iNOS 的表达增加，但内皮一氧化氮合酶的表达没有改变。我们的研究结果表明，百草枯中毒会增加内皮细胞 iNOS 的表达和基础 NO 的产生，从而降低肺血管对血管收缩剂的反应性。因此，我们的结果不支持这样的假设，即百草枯诱导的 ALI 中的肺动脉高压是由内皮细胞 NO 产生减少或肺血管收缩性增加介导的。
