Lipopolysaccharide (LPS) is implicated in many pulmonary and airway inflammatory diseases. Tachykinins released from nerve endings increase vascular permeability. In this study, we have assessed the enhancement by LPS of tachykinin-mediated plasma exudation in guinea-pig airways, and examined the role of oxidants as well as leukocyte adherence.LPS (100 μg kg−1, i.v.) was administered 0–3 h before bilateral electrical stimulation of the cervical vagus nerves in animals anaesthetized with urethane and ventilated. Vagal stimulation increased vascular permeability in the airways. LPS enhanced the vagally-mediated plasma exudation with the peak effect at 1 h after LPS administration. LPS alone induced no significant plasma exudation. LPS also enhanced exogenous substance P (10−8 mol kg−1, i.v.)-induced plasma exudation.The NK-1 receptor antagonist L-732,138 abolished vagally-induced plasma exudation and significantly inhibited the enhancement by LPS. Pretreatment with superoxide dismutase (SOD, 5000 U kg−1, i.p.) did not affect the vagally-induced plasma exudation, but inhibited the LPS-enhanced neurogenic plasma leakage. The LPS-enhanced vagally-induced plasma exudation was not completely inhibited by either L-732,138 or SOD pretreatment alone, but was blocked by the combination of both pretreatments.Neutrophil depletion by cyclophosphamide alone did not influence vagally-induced plasma exudation, but significantly inhibited the LPS-enhanced response.In conclusion, we have demonstrated LPS enhanced neurogenic plasma exudation by augmenting the response to tachykinins, partly through NK-1 receptors, to directly increase vascular permeability or to enhance leukocyte adhesion-mediated endothelial cell injury. Tachykinins released from nerve endings may contribute to endotoxin-related airway inflammatory responses.
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机译:脂多糖(LPS)与许多肺部和气道炎性疾病有关。从神经末梢释放的速激肽可增加血管通透性。在这项研究中,我们评估了豚鼠气道中速激肽介导的血浆渗出液通过LPS的增强作用,并研究了氧化剂和白细胞粘附的作用。LPS(100μgkg-1,iv)给药0-3在用尿烷麻醉并通气的动物对颈迷走神经进行双侧电刺激前h。迷走神经刺激增加了呼吸道的血管通透性。 LPS增强了阴道介导的血浆渗出,在LPS给药后1 h达到峰值。单独的LPS不会引起明显的血浆渗出。 LPS还增强了外源性物质P(10-8μmol·kg-1,i.v.)诱导的血浆渗出.NK-1受体拮抗剂L-732,138消除了阴道诱导的血浆渗出,并显着抑制了LPS引起的血浆渗出。用超氧化物歧化酶(SOD,5000 U kg-1,i.p.)预处理不会影响阴道诱发的血浆渗出,但会抑制LPS增强的神经源性血浆渗漏。 L-732,138或SOD预处理均不能完全抑制LPS增强的阴道诱发的血浆渗出,但两种预处理的组合均能阻止LPS增强的阴道分泌。总之,我们证明了LPS通过增加对速激肽的反应(部分通过NK-1受体)来增强神经速动性血浆渗出,从而直接增加血管通透性或增强白细胞粘附介导的内皮细胞损伤。从神经末梢释放的速激肽可能与内毒素相关的气道炎症反应有关。
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