NITRIC-OXIDE AS A MEDIATOR OF OXIDANT LUNG INJURY DUE TO PARAQUAT
NITRIC-OXIDE AS A MEDIATOR OF OXIDANT LUNG INJURY DUE TO PARAQUAT
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DOI：
10.1073/pnas.91.16.7445
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发表时间：
1994-08-02
影响因子：
11.1
通讯作者：
SAID, SI
中科院分区：
文献类型：
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作者：
BERISHA, HI;PAKBAZ, H;SAID, SI
在低浓度下，一氧化氮是一种生理递质，但在过高浓度下，它可能导致细胞和组织损伤。我们报告说，在急性氧化损伤诱导的除草剂百草枯在离体豚鼠肺，一氧化氮的合成显着刺激，证明肺灌流液中的环鸟苷酸和亚硝酸盐和L-瓜氨酸的生产在肺组织中的水平增加。所有的损伤迹象，包括气道和灌注压增加，肺水肿，和蛋白质泄漏到空气空间，剂量依赖性衰减或完全防止由N-G-硝基-L-精氨酸甲酯或N-ω-硝基-L-精氨酸，选择性和竞争性抑制剂的一氧化氮合酶。保护作用被过量的L-精氨酸逆转，但不被其对映体D-精氨酸逆转。当血液被添加到肺灌流液中时，百草枯损伤被缓和或延迟，就像百草枯被给予麻醉的豚鼠时一样。损伤的快速发作和其未能发生在Ca 2+的情况下表明，组成型而不是诱导型一氧化氮合酶负责刺激的一氧化氮合成。研究结果表明，一氧化氮在百草枯引起的肺组织损伤中起着关键作用，它可能是其他形式的氧化性组织损伤的致病因素。
At low concentrations, nitric oxide is a physiological transmitter, but in excessive concentrations it may cause cell and tissue injury. We report that in acute oxidant injury induced by the herbicide paraquat in isolated guinea pig lungs, nitric oxide synthesis was markedly stimulated, as evidenced by increased levels of cyclic GMP in lung perfusate and of nitrite and L-citrulline production in lung tissue. All signs of injury, including increased airway and perfusion pressures, pulmonary edema, and protein leakage into the airspaces, were dose-dependently attenuated or totally prevented by either N-G-nitro-L-arginine methyl ester or N-omega-nitro-L-arginine, selective and competitive inhibitors of nitric oxide synthase. Protection was reversed by excess L-arginine but not by its enantiomer D-arginine. When blood was added to the lung perfusate, the paraquat injury was moderated or delayed as it was when paraquat was given to anesthetized guinea pigs. The rapid onset of injury and its failure to occur in the absence of Ca2+ suggest that constitutive rather than inducible nitric oxide synthase was responsible for the stimulated nitric oxide synthesis. The findings indicate that nitric oxide plays a critical role in the production of lung tissue injury due to paraquat, and it may be a pathogenetic factor in other forms of oxidant tissue injury.