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

J Biomed Sci. 2005;12(4):671-81. doi: 10.1007/s11373-005-7892-x. Epub 2005 Nov 10.


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-kappaB (NF-kappaB) 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 H(2)O(2) ROS amount. L-732138 (NK(1) receptor antagonist), SR-48968 (NK(2) receptor antagonist), dimethylthiourea (H(2)O(2) scavenger) or catechins (O (2)(-) and H(2)O(2) scavenger) pretreatment reduced efferent TVN stimulation-enhanced hypotension, bronchoconstriction, and plasma extravasation. Increased frequency of TVN stimulation significantly upregulated the expression of nuclear factor-kappaB (NF-kappaB) in nuclear protein and intercellular adhesion molecule-1 (ICAM-1) in total protein of the lower respiratory tract tissue. The upregulation of NF-kappaB and ICAM-1 was attenuated by NK receptor antagonist and antioxidants. In conclusion, TVN efferent stimulation increases substance P release to trigger NF-kappaB mediated ICAM-1 expression and O (2)(-) and H(2)O(2) ROS production in the respiratory tract.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Blood Vessels / pathology
  • Bronchoconstriction*
  • Carbon / pharmacology
  • Electric Stimulation Therapy / methods*
  • Electromyography
  • Endothelium, Vascular / metabolism
  • Immunoblotting
  • Inflammation*
  • Intercellular Adhesion Molecule-1 / metabolism
  • Luminol / chemistry
  • Male
  • Myocytes, Smooth Muscle / cytology
  • NF-kappa B / metabolism
  • Neurons, Efferent / pathology*
  • Oxidative Stress*
  • Oxygen / chemistry
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species
  • Respiratory System / metabolism
  • Respiratory System / pathology*
  • Silver Staining
  • Substance P / pharmacology*
  • Tachykinins / antagonists & inhibitors
  • Up-Regulation
  • Vagus Nerve / pathology*


  • Antioxidants
  • NF-kappa B
  • Reactive Oxygen Species
  • Tachykinins
  • chinese ink
  • Intercellular Adhesion Molecule-1
  • Substance P
  • Luminol
  • Carbon
  • Oxygen