组成型一氧化氮合成酶及其酪氨酸磷酸化过程对LPS介入的鼠肺动脉张力的调节作用

目的 研究组成型NO合成酶及其酪氨酸磷酸化过程对LPS介入的鼠肺动脉张力的影响。方法 将取自Sprague-Dawley鼠的肺动脉环悬挂在含有Krebs溶液的游离器官槽中以备作血管反应实验之用。结果 经LPS处理的肺动脉环对去氧肾上腺素的收缩反应明显降低，但此反应的减弱可以被L-NAME，非选择性NO合成酶抑制剂和7-NINA，选择性神经元NO合成酶抑制剂弥补。LPS同时可以降低肺功能对乙酰胆碱的内皮依赖舒张反应，但此减弱由于钒酸钠，选择性酪氨酸磷酸酶抑制剂的存在而缓解，结论 神经元NO合成酶参与了LPS介入的NO过度产生而形成的肺动脉张力降低，而在这个过程中，内皮NO合成酶的催化活性是受损的，但这种损害因触发了另一种通过酪氨酸磷酸化途径的内皮依赖舒张反应而得到补偿。

Role of constitutive NO synthase and its tyrosine phosphorylation in the regulation of pulmonary vascular tone after LPS

Objective To study the effects of constitutive NO synthase (NOS) and its tyrosine phosphorylation in the regulation of pulmonary vascular tone mediated by LPS.Methods Polmonary artery (PA) rings were dissected from Sprague-Dawley rats,suspended in organ bathes containing Krebs solution,and tested for vascular reactivity.Results Pretreatment of PA rings with LPS significantly decreased contractile response to phenylephrine.The loss of contractility of PA rings was however restored by L-NAME,a general inhibitor of NOS and 7-NINA,a specific inhibitor of neuronal NOS (nNOS).LPS also reduced the endothelium-dependent relaxation in response to acetylcholine.However,after exposure to LPS,PA rings incubated with sodium orthovanadate,a selective inhibitor of tyrosine phophatase showed a significant increase in the maximal relaxant response to acetylcholine.Conclusions nNOS play an important role in LPS-induced pulmonary vascular hyporeactivity through stimulating excess production of NO.Inhibition of endothelial NOS(eNOS) of PA rings could be compensated by a complex mechanism via tyrosine phosphorylation pathway.