title: Thoracic vagal efferent nerve stimulation evokes substance P-induced early airway bronchonstriction and late proinflammatory and oxidative injury in the rat respiratory tract.
abstract: 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.
authors.affiliation: Department of Biological Science, National Sun Yat-Sen University, Kaohsiung, ROC.
authors.forename: Ping-Chia
authors.initials: PC
authors.lastname: Li
authors.forename: Sheng-Chung
authors.initials: SC
authors.lastname: Li
authors.forename: Yuan-Ju
authors.initials: YJ
authors.lastname: Lin
authors.forename: Jin-Tung
authors.initials: JT
authors.lastname: Liang
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chien
authors.forename: Chen-Fu
authors.initials: CF
authors.lastname: Shaw
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001808:Blood Vessels / Q000473:pathology; D016084:Bronchoconstriction; D002244:Carbon / Q000494:pharmacology; D004599:Electric Stimulation Therapy / Q000379:methods*; D004576:Electromyography; D004730:Endothelium, Vascular / Q000378:metabolism; D015151:Immunoblotting; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008165:Luminol / Q000737:chemistry; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D016328:NF-kappa B / Q000378:metabolism; D009476:Neurons, Efferent / Q000473:pathology*; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D012137:Respiratory System / Q000378:metabolism / Q000473:pathology*; D016622:Silver Staining; D013373:Substance P / Q000494:pharmacology*; D015320:Tachykinins / Q000037:antagonists & inhibitors; D015854:Up-Regulation; D014630:Vagus Nerve / Q000473:pathology*
chemical_list: D000975:Antioxidants; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D015320:Tachykinins; C028433:chinese ink; D018799:Intercellular Adhesion Molecule-1; D013373:Substance P; D008165:Luminol; D002244:Carbon; D010100:Oxygen