Neurogenic inflammatory responses can be induced by antidromic electrical stimulation or intravenous capsaicin injection. These responses were thought to be caused by neuropeptides released from the sensory axon of C-fiber nerve endings. The relation of tachykinins, reactive oxygen species (ROS) and reactive nitrogen species (RNS) on electrical stimulation of thoracic vagus nerve (TVNS) or capsaicin-evoked neurogenic inflammation in respiratory tract of atropine-treated rats was not clear. In the present studies, the role of ROS and RNS on neurogenic inflammation were investigated in TVNS and capsaicin injected rats.
The experiments were divided into two parts. In the first part, TVNS was performed by thoracotomy, non-cholinergic regulation of neurogenic plasma extravasation in the trachea and bronchi were examined, and whether TVNS via NK receptor facilitates neurogenic inflammation by nuclear factor-kappaB (NF-£eB) activation and ROS production were expored. Our results in this part showed that TVNS evoked substance P release, hypotension, bronchoconstriction (as shown by increases in smooth muscle electromyographic activity and total pulmonary resistance), trachea plasma extravasation as well as increases in blood O2- and H2O2 ROS amount in a frequency-dependent manner. Histopathological examination demonstrated silver-stained leaky venules, India-ink labeled plasma extravasation, and accumulations of inflammatory cells in the right lower trachea after TVNS. L-732138 (NK1 receptor antagonist), SR-48968 (NK2 receptor antagonist), dimethylthiourea (H2O2 scavenger) or catechins (O2- and H2O2 scavenger) pretreatment reduced TVNS-enhanced hypotension, bronchoconstriction, and plasma extravasation. TVNS upregulated the expression of NF-£eB in nuclear protein and intercellular adhesion molecule-1 (ICAM-1) in total protein of the lower respiratory tract tissue in a frequency-dependent manner. The upregulation of NF-£eB and ICAM-1 was attenuated by NK receptor antagonist and antioxidants. In the second part, the contribution of nitric oxide (NO) to capsaicin-evoked airway responses was investigated in rats. The measurement of plasma NO level, airway dynamics, airway smooth muscle electromyogram, and plasma extravasation by India ink and Evans blue leakage technique was adapted. Our results in this part showed that capsaicin injection evoked hypotension, bronchoconstriction, trachea plasma extravasation as well as increases in plasma NO level in a dose-dependent manner. L-732138 or SR-48968 pretreatment reduced capsaicin-enhanced hypotension, bronchoconstriction, plasma extravasation, and plasma NO level. Inhibition of a non-selective NO synthase (NOS) inhibitor (NG-nitro-L-Arginine methyl ester, L-NAME), or a selective inducible NO synthase (iNOS) inhibitor (aminoguanidine), reduced capsaicin-induced increases in plasma NO level and protected against capsaicin-induced plasma extravasation, whereas L-arginine (a NO precursor), enhances capsaicin-evoked plasma NO level and plasma extravasation. L-Arginine pretreatment ameliorated capsaicin-induced bronchoconstriction, whereas L-NAME and aminoguanidine exaggerated capsaicin-induced bronchoconstriction.
In summary, both TVNS and capsaicin injection may increase oxidative stress responses. TVNS enhances proinflammatory NF-£eB and ICAM-1 expression, increases the production of O2- and H2O2 activity in the respiratory tract of atropine-treated rats. Pretreatment with antioxidants and selective NK receptor antagonists attenuate TVNS evoked airway hyperactivity, proinflammatory response, and oxidative stress. Capsaicin injection stimulates the release of tachykinins, which act on NK1 and NK2 receptors located on the smooth muscles of airways and blood vessels. The interaction of NK receptors with tachykinin enhances furtherly the NO formation, bronchoconstriction, vasodilation, and plasma extravasation in the trachea. The released tachykinins also increase the production of NO via iNOS, and iNOS -evoked NO counteracts tachykinin-mediated bronchoconstriction, but exacerbates tachykinin-mediated plasma extravasation.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0119106-105855 |
| Date | 19 January 2006 |
| Creators | Li, Ping-chia |
| Contributors | Tzer-bin Lin, Chen -fu Shaw, Mo Kuo, David-Chao, Chiang-ting Chien, Ji-chuu Hwang |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | Cholon |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0119106-105855 |
| Rights | campus_withheld, Copyright information available at source archive |
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