Thoracic vagal efferent nerve stimulation evokes substance P-induced early airway bronchonstriction and late proinflammatory and oxidative injury in the rat respiratory tract.
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.
Li
Ping-Chia
PC
Department of Biological Science, National Sun Yat-Sen University, Kaohsiung, ROC.
Li
Sheng-Chung
SC
Lin
Yuan-Ju
YJ
Liang
Jin-Tung
JT
Chien
Chiang-Ting
CT
Shaw
Chen-Fu
CF
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*
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