Tachykinins and airway microvascular leakage induced by HCl intra-oesophageal instillation
Tachykinins and airway microvascular leakage induced by HCl intra-oesophageal instillation
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DOI：
10.1183/09031936.02.00250902
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发表时间：
2002-08-01
影响因子：
24.3
通讯作者：
Advenier, C
中科院分区：
文献类型：
--
作者：
Daoui, S;D'Agostino, B;Advenier, C
胃食管反流是一种常见的临床疾病，伴有多种呼吸道症状，包括慢性咳嗽和哮喘加重。在本研究中，通过检查速激肽NK 1和NK 3受体拮抗剂（分别为SR 140333和SR 142801）（1-10 www.example.com（-1））对食道中注入盐酸（HCl）诱导的气道蛋白质渗出的影响，在豚鼠和兔中检查了酸诱导速激肽释放的潜在作用mg.kg。豚鼠用氨基甲酸乙酯麻醉，用Hypnorm进行神经镇痛。通过测量伊文思蓝染料外渗来评估气道血管渗漏。所有动物均接受阿托品预处理（1 mg.kg（-1））。i.p.），普萘洛尔（mg.kg（-1）i. p.），磷酰胺（2.5 mg.kg（-1）i. v.）和盐水或速激肽受体拮抗剂（1-10 mg.kg（-1）i. p.）。将1 N HCl输注到食管中导致主支气管和气管中的血浆外渗分别增加3倍和5倍。这种增加在很大程度上被速激肽NK 1和NK 3受体拮抗剂SR 140333和SR 142801阻止（1-10 mg.kg（-1））。这些结果表明，由食管内HCl输注诱导的气道中的蛋白质外渗主要依赖于速激肽的释放，并且涉及NK 1和NK 3速激肽受体。结果表明，盐酸诱导的感觉神经刺激可能会在中间神经元和/或神经节，其中NK 3受体已被证明发挥重要作用的周边。
Gastro-oesophageal reflux is a common clinical disorder associated with a variety of respiratory symptoms, including chronic cough and exacerbation of asthma. In this study, the potential role of acid-induced tachykinin release was examined in guinea pigs and rabbits, by examining the effects of the tachykinin NK1 and NK3 receptors antagonists (SR 140333 and SR 142801, respectively) (1-10 mg.kg(-1)) on plasma protein extravasation induced in airway's by hydrochloric acid (HCl) infusion in the oesophagus.Guinea pigs were anaesthetised with urethane, while rabbits were subject to neuroleptoanalgesia with hypnorm. Airway vascular leakage was evaluated by measuring extravasation of Evans blue dye. All animals were pretreated with atropine (1 mg.kg(-1). i.p.), propranolol (1 mg.kg(-1) i.p.), phosphoramidon (2.5 mg.kg(-1) i.v.) and saline or tachykinin receptor antagonists (1-10 mg.kg(-1) i.p.).Infusion of 1 N HCl into the oesophagus led to a three- and five-fold increase in plasma extravasation in the main bronchi and trachea, respectively. This increase was largely prevented by the tachykinin NK1 and NK3 receptor antagonists SR 140333 and SR 142801 (1-10 mg.kg(-1)).These results suggest that protein extravasation in the airways, as induced by intra-oesophageal HCl infusion, is mainly dependent on the release of tachykinins, and that both NK1 and NK3 tachykinin receptors are involved. The results suggest that HCl-induced sensory nerve stimulation may act in the periphery on intermediate neurons and/or ganglia where NK3 receptors have been shown to play an important role.