A SUBSTANCE-P ANTAGONIST INHIBITS VAGALLY INDUCED INCREASE IN VASCULAR-PERMEABILITY AND BRONCHIAL SMOOTH-MUSCLE CONTRACTION IN THE GUINEA-PIG
A SUBSTANCE-P ANTAGONIST INHIBITS VAGALLY INDUCED INCREASE IN VASCULAR-PERMEABILITY AND BRONCHIAL SMOOTH-MUSCLE CONTRACTION IN THE GUINEA-PIG
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DOI：
10.1073/pnas.80.4.1120
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发表时间：
1983-01-01
期刊：
影响因子：
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通讯作者：
FOLKERS, K
中科院分区：
文献类型：
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作者：
LUNDBERG, JM;SARIA, A;FOLKERS, K
电刺激麻醉豚鼠的颈迷走神经可引起呼吸吹入压迅速增加，表明气道阻力增加。静脉注射P物质（SP）拮抗剂[D-Arg 1，D-Pro 2，D-Trp 7，9，Leu 11]SP后，对迷走神经刺激的充气压力反应降低78%，而心血管效应无变化。组胺受体阻断剂用于抑制SP拮抗剂诱导的组胺释放效应。[D-Arg 1，D-Pro 2，D-Trp 7，9，Leu 11]SP也可降低静脉注射SP或辣椒素引起的吹入压升高。场刺激引起的主支气管和肺门支气管的长时间非胆碱能收缩，以及SP和辣椒素的收缩作用，也被SP拮抗剂阻断。离体气管胆碱能收缩和非胆碱能舒张均不被拮抗剂阻断。迷走神经刺激在体内也增加了呼吸道和食管的血管通透性，引起上皮下水肿，如伊文思蓝外渗所示。预先用[D-Arg 1，D-Pro 2，D-Trp 7，9，Leu 11]SP处理抑制迷走神经刺激和外源性SP诱导的通透性增加。显然，迷走神经或辣椒素诱导的支气管平滑肌张力增加的主要部分是由感觉神经元释放SP引起的。激活迷走含SP的感觉神经引起局部水肿。因此，在正常和病理生理条件下，气管支气管传入含SP的C纤维可以对平滑肌张力和血管通透性进行局部控制。
Electrical stimulation of the cervical vagus nerve in anesthetized guinea pigs induced a rapid increase in respiratory insufflation pressure, suggesting increased airway resistance. After i.v. administration of a substance P (SP) antagonist, [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP, the insufflation pressure response to vagal stimulation was reduced by 78% while the cardiovascular effects were unchanged. Histamine receptor-blocking agents were used to inhibit the effects of histamine release induced by the SP-antagonist. [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP also reduced the increase in insufflation pressure caused by i.v. SP or capsaicin. The long-lasting noncholinergic contraction of the main and hilus bronchi induced by field stimulation in vitro, as well as the contractile effects of SP and capsaicin, were also blocked by the SP antagonist. The cholinergic contractions and the noncholinergic tracheal relaxation on field stimulation in vitro were not blocked by the antagonist. Vagal stimulation in vivo also increased vascular permeability in the respiratory tract and esophagus, causing a subepithelial edema as indicated by Evans blue extravasation. Previous treatment with [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP inhibited the permeability increase induced by both vagus nerve stimulation and exogenous SP. SP release from vagal sensory nerves was indirectly shown by reduction in the bronchial levels of SP after nerve stimulation in vivo. Apparently a major portion of the vagally or capsaicin-induced increase in bronchial smooth muscle tone is caused by SP release from sensory neurons. Activation of vagal SP-containing sensory nerves induced local edema. Tracheobronchial afferent SP-containing C fibers may thus exert local control of smooth muscle tone and vascular permeability in normal and pathophysiological conditions.