Skip to main content

Advertisement

Log in

Thoracic Vagal Efferent Nerve Stimulation Evokes Substance P-Induced Early Airway Bronchonstriction and Late Proinflammatory and Oxidative Injury in the Rat Respiratory Tract

  • Published:
Journal of Biomedical Science

Summary

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Baluk, P., Gabella, G. (1989) "Innervation of the guinea pig trachea: a quantitative morphological study of intrinsic neurons and extrinsic nerves" J. Comp. Neurol. 285: 117-132

    Article  PubMed  CAS  Google Scholar 

  2. Belvisi, M.G. (2002) "Overview of the innervation of the lung" Curr. Opin. Pharmacol. 2: 235-243

    Article  PubMed  Google Scholar 

  3. Coleridge, H.M., Coleridge, J.C.G. (1994) "Pulmonary reflexes: neural mechanisms of pulmonary defence" Annu. Rev. Physiol. 56: 69-91

    Article  PubMed  CAS  Google Scholar 

  4. Kincy-Cain, T., Bost, K.L. (1997) "Substance P-induced IL-12 production by murine macrophages" J. Immunol. 158: 2334-2339

    PubMed  CAS  Google Scholar 

  5. Chien, C.T., Yu, H.J., Lin, T.B., LaiMK. Hsu, S.M. (2003) "Substance P via NK1 receptor facilitates hyperactive bladder afferent signaling via action of ROS" Am. J. Physiol. Renal. Physiol. 284: F840-F851

    PubMed  CAS  Google Scholar 

  6. McDonald, D.M. (1987) "Neurogenic inflammation in the respiratory tract: actions of sensory nerve mediators on blood vessels and epithelium of the airway mucosa" Am. Rev. Respir. Dis. 136: S65-S72

    PubMed  CAS  Google Scholar 

  7. Yu H.J., Lin B.R., Lee H.S., Shun C.T., Yang C.C., Lai T.Y., Chien C.T. and Hsu S.M., Sympathetic vesicovascular reflex induced by acute urinary retention evokes proinflammatory and proapoptotic injury in rat livers. Am. J. Physiol. Renal Physiol. 2005. In press

  8. DeRose, V., Robbins, R.A., Snider, R.M., Spurzem, J.R., Thiele, G.M., Rennard, S.I., Rubinstein, I. (1994) "Substance P increases neutrophil adhesion to bronchial epithelial cells" J. Immunol. 152: 1339-1346

    PubMed  CAS  Google Scholar 

  9. Nakagawa, N., Iwamoto, I., Yoshida, S. (1993) "Effect of substance-P on the expression of an adhesion molecule ICAM-1 in human vascular endothelial cells" Regul. Pept. 46: 223-224

    Article  PubMed  CAS  Google Scholar 

  10. Wang, S.Z., Hallsworth, P.G., Dowling, K.D., Alpers, J.H., Bowden, J.J., Forsyth, K.D. (2000) "Adhesion molecule expression on epithelial cells infected with respiratory syncytial virus" Eur. Respir. J. 15: 358-366

    Article  PubMed  CAS  Google Scholar 

  11. Chen, W.C., Hayakawa, S., Shimizu, K., Chien, C.T., Lai, M.K. (2004) "Catechins prevents substance P-induced hyperactive bladder in rats via the downregulation of ICAM and ROS" Neurosci. lett. 367: 213-217

    Article  PubMed  CAS  Google Scholar 

  12. Joos, G.F., Germonpré, P.R., Pauwels, R.A. (2000) "Role of tachykinins in asthma" Allergy 55: 321-337

    Article  PubMed  CAS  Google Scholar 

  13. Wood, L.G., Gibson, P.G., Garg, M.L. (2003) "Biomarker of lipid peroxidation, airway inflammation and asthma" Eur. Respir. J. 21: 177-186

    Article  PubMed  CAS  Google Scholar 

  14. Begg, A.A., Sha, W.C., Bronson, R.T., Ghosh, S., Baltimore, D. (1995) "Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-κB" Nature 376: 167-170

    Article  PubMed  Google Scholar 

  15. Hart, L.A., Krishnan, V.L., Adcock, I.M., Barnes, P.J., Chung, K.F. (1998) "Activation and localization of transcription factor, nuclear factor-κB, in asthma" Am. J. Respir. Crit. Care Med. 158: 1585-1592

    PubMed  CAS  Google Scholar 

  16. Natarajan, R., Fisher, B.J., Jones, D.G., Fowler, A.A., III (2002) "Atypical mechanism of NF-κB activation during reoxygenation stress in microvascular endothelium: a role for tyrosine kinases" Free Radic. Biol. Med. 33: 962-973

    Article  PubMed  CAS  Google Scholar 

  17. Nagata, M., Sedgwick, J.B., Kita, H., Busse, W.W. (1998) "Granulocyte macrophage colony-stimulating factor augments ICAM-1 and VCAM-1 activation of eosinophil function" Am. J. Respir. Cell Mol. Biol. 19: 158-166

    PubMed  CAS  Google Scholar 

  18. Hwang, T., Huang, H.T., Tsao, C.F. (1999) "Thoracic vagus section distal to the recurrent laryngeal nerve reduces substance P-immunoreactive innervation in the rat bronchial tree" Anal. Embryol. 200: 153-160

    Article  CAS  Google Scholar 

  19. Hua, F., Ardell, J.L., Williams, C.A. (2004) "Left vagal stimulation induces dynorphin release and suppresses substance P release from the rat thoracic spinal cord during cardiac ischemia" Am. J. Physiol. Regul. Integr. Comp. Physiol. 287: R1468-R1477

    PubMed  CAS  Google Scholar 

  20. Li, P.C., Huang, H.T., Liang, J.T. (2001) "Neurophysiology effects of recurrent laryngeal and thoracic vagus nerves on mediating the neurogenic inflammation of the trachea, bronchi, and esophagus of rats" Auton. Neurosci. Basic. Clin. 88: 142-150

    Article  CAS  Google Scholar 

  21. Rao, P.S., Rujikarn, N., Luber, J.M., Jr (1988) "High-performance liquid chromatographic method for the direct quantitation of oxyradicals in myocardium and blood by means of 1,3-dimethylthiourea and dimethyl sulfoxide" J. Chromatogr. 459: 269-273

    Article  PubMed  CAS  Google Scholar 

  22. Li, P.C., Shaw, C.F., Kuo, T.F., Chien, C.T. (2005) "Inducible nitric oxide synthase evoked nitric oxide counteracts capsaicin-induced airway smooth muscle contraction, but exacerbates plasma extravasation" Neurosci. lett. 378: 117-122

    Article  PubMed  CAS  Google Scholar 

  23. Lotz, M., Vaughan, J.H., Carson, D.A. (1988) "Effect of neuropeptides on production of inflammatory cytokines by human monocytes" Science 241: 1218-1221

    Article  PubMed  CAS  Google Scholar 

  24. Quinlan, K.L., Naik, S.M., Cannon, G., Armstrong, C.A., Bunnett, N.W., Ansel, J.C., Caughman, S.W. (1999) "Substance P activates coincident NF-AT- and NF-B-dependent adhesion molecule gene expression in microvascular endothelial cells through intracellular calcium mobilization" J. Immunol. 163: 5656-5665

    PubMed  CAS  Google Scholar 

  25. Birder, L.A., Kanai, A.J., Groat, W.C., Kiss, S., Nealen, M.L., Burke, N.E., Dineley, K.E., Watkins, S., Reynolds, L.J., Caterina, M.J. (2001) "Vanilloid receptor expression suggests a sensory role for urinary bladder epithelial cells" Proc. Natl. Acad. Sci. 98: 13396-13401

    Article  PubMed  CAS  Google Scholar 

  26. Bertrand, C., Nadel, J.A., Graf, P.D., Geppetti, P. (1993) "Capsaicin increases airflow resistance in guinea pigs in vivo by activating both NK2 and NK1 tachykinin receptors" Am. Rev. Respir. Dis. 148: 909-914

    PubMed  CAS  Google Scholar 

  27. Cuesta, M.C., Quintero, L., Pons, H., Suarez-Roca, H. (2002) "Substance P and calcitonin gene-related peptide increase IL-1, IL-6 and TNF-α secretion from human peripheral blood mononuclear cells" Neurochem. Int. 40: 301-306

    Article  PubMed  CAS  Google Scholar 

  28. Suzuke, H., Miura, S., Liu, Y.Y., Tsuchiya, M., Ishii, H. (1995) "Substance P induces degranulation of mast cells and leukocyte adhension to venular endothelium" Peptides 16: 1447-1452

    Article  PubMed  Google Scholar 

  29. Chien, C.T., Yu, H.J., Lin, C.F., Chen, C.F. (2000) "Neural mechanisms of impaired micturition reflex in rats with acute partial bladder outlet obstruction" Neuroscience 96: 221-230

    Article  PubMed  CAS  Google Scholar 

  30. Bauer, V., Sotnikovia, R., Machova, J., Matyas, S., Pucovsky, V., Stefek, M. (1999) "Reactive oxygen species induced smooth muscle responses in the intestine, vessels and airways and the effect of antioxidants" Life Sci. 65: 1909-1917

    Article  PubMed  CAS  Google Scholar 

  31. Horakova, L., Stolc, S. (1998) "Antioxidant and pharmacodynamic effects of pyridoindole stobadine" Gen. Pharmacol. 30: 627-638

    Article  PubMed  CAS  Google Scholar 

  32. Chen, X.L., Zhang, Q., Zhao, R., Ding, X., Tummala, P.E., Medford, R.M. (2003) "Rac1 and superoxide are required for the expression of cell adhesion molecules induced by tumor necrosis factor-α in endothelial cells" J. Pharmacol. Exp. Ther. 305: 573-580

    Article  PubMed  CAS  Google Scholar 

  33. Paxian, M., Bauer, I., Kaplan, D., Bauer, M., Rensing, H. (2002) "Hepatic redox regulation of transcription factors activator protein-1 and nuclear factor-κB after hemorrhagic shock in vivo " Antioxid Redox Signal 4: 711-720

    Article  PubMed  CAS  Google Scholar 

  34. Quinlan, K.L., Song, I.-S., Bunnett, N.W. (1998) "Neuropeptide regulation of human dermal microvascular endothelial cell ICAM-1 expression and function" Am. J. Physiol. 275: C1580-C1590

    PubMed  CAS  Google Scholar 

  35. Michiels, C., Minet, E., Mottet, D., Raes, M. (2002) "Regulation of gene expression by oxygen: NF-κB and HIF-1, two extremes" Free Radic. Biol. Med. 33: 1231-1242

    Article  PubMed  CAS  Google Scholar 

  36. Bowie, A.G., O'Neill, L.A. (2000) "Oxidative stress and nuclear factor-κB activation" Biochem. Pharmacol. 59: 13-23

    Article  PubMed  CAS  Google Scholar 

  37. Scalia, R., Lefer, A.M. (1998) " In vivo regulation of PECAM-1 activity during acute endothelial dysfunction in the rat mesenteric microvasculature" J. Leukoc. Biol. 64: 163-169

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Chiang-Ting Chien.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, PC., Li, SC., Lin, YJ. et al. 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 12, 671–681 (2005). https://doi.org/10.1007/s11373-005-7892-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11373-005-7892-x

Keywords

Navigation