Thoracic vagal efferent nerve stimulation evokes substance P-induced early airway bronchonstriction and late proinflammatory and oxidative injury in the rat respiratory tract

Ping Chia Li, Sheng Chung Li, Yuan Ju Lin, Jin Tung Liang, Chiang Ting Chien, Chen Fu Shaw

Research output: Contribution to journalArticle

12 Citations (Scopus)


Electrical stimulation of efferent thoracic vagus nerve (TVN) evoked neurogenic inflammation in respiratory tract of atropine-treated rats by an undefined mechanism. We explored whether efferent TVN stimulation via substance P facilitates neurogenic inflammation via action of nuclear factor-κB (NF-κB) activation and reactive oxygen species (ROS) production. Our results showed that increased frequency of TVN stimulation concomitantly increased substance P-enhanced hypotension, and bronchoconstriction (increases in smooth muscle electromyographic activity and total pulmonary resistance). The enhanced SP release evoked the appearance of endothelial gap in silver-stained leaky venules, India-ink labeled extravasation, and accumulations of inflammatory cells in the respiratory tract, contributing to trachea plasma extravasation as well as increases in blood O 2- and H2O2 ROS amount. L-732138 (NK1 receptor antagonist), SR-48968 (NK2 receptor antagonist), dimethylthiourea (H2O2 scavenger) or catechins (O 2- and H2O2 scavenger) pretreatment reduced efferent TVN stimulation-enhanced hypotension, bronchoconstriction, and plasma extravasation. Increased frequency of TVN stimulation significantly upregulated the expression of nuclear factor-κB (NF-κB) in nuclear protein and intercellular adhesion molecule-1 (ICAM-1) in total protein of the lower respiratory tract tissue. The upregulation of NF-κB and ICAM-1 was attenuated by NK receptor antagonist and antioxidants. In conclusion, TVN efferent stimulation increases substance P release to trigger NF-κB mediated ICAM-1 expression and O 2- and H2O2 ROS production in the respiratory tract.

Original languageEnglish
Pages (from-to)671-681
Number of pages11
JournalJournal of Biomedical Science
Issue number4
Publication statusPublished - 2005 Jul 1



  • Intercellular adhesion molecule-1
  • Nuclear factor-κB
  • Reactive oxygen species
  • Substance P
  • Thoracic vagus nerve

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Pharmacology (medical)

Cite this