Involvement of endogenous hydrogen sulfide in cigarette smoke-induced changes in airway responsiveness and inflammation of rat lung

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2011-03, Vol.53 (3), p.334-341
• Main Authors: Chen, Ya-Hong, Wang, Pei-Pei, Wang, Xin-Mao, He, Yan-Jing, Yao, Wan-Zhen, Qi, Yong-Fen, Tang, Chao-Shu
• Format: Article
• Language: English
• Subjects: acetylcholine; Acetylcholine - pharmacology; Airway hyper-responsiveness; Airway inflammation; Airway smooth muscle; Alkynes - pharmacology; animal models; Animals; anti-inflammatory activity; blood serum; chronic exposure; Chronic obstructive pulmonary disease; cigarettes; Cystathionine gamma-Lyase - antagonists & inhibitors; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; epithelium; glibenclamide; Glycine - analogs & derivatives; Glycine - pharmacology; Hydrogen sulfide; Hydrogen Sulfide - blood; Hydrogen Sulfide - metabolism; In Vitro Techniques; inflammation; Inflammation - blood; Inflammation - etiology; interleukin-8; Interleukin-8 - metabolism; Lung - drug effects; Lung - metabolism; Lung - pathology; Male; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Muscle, Smooth - physiology; Nicotiana - chemistry; potassium chloride; protein synthesis; Random Allocation; Rats; Rats, Sprague-Dawley; Respiratory Hypersensitivity - blood; Respiratory Hypersensitivity - etiology; Smoke - adverse effects; smooth muscle; sodium; Sulfides - pharmacology; Trachea - drug effects; Trachea - physiology; Tumor Necrosis Factor-alpha - metabolism; Vasodilator Agents - pharmacology
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2010.12.006

Hydrogen sulfide (H 2S), recently considered the third endogenous gaseous transmitter, may have an important role in systemic inflammation. We investigated whether endogenous H 2S may be a crucial mediator in airway responsiveness and airway inflammation in a rat model of chronic exposure to cigarette smoke (CS). Rats randomly divided into control and CS-exposed groups were treated with or without sodium hydrosulfide (NaHS, donor of H 2S) or propargylglycine (PPG, inhibitor of cystathionine-γ-lyase [CSE], an H 2S-synthesizing enzyme) for 4-month exposure. Serum H 2S level and CSE protein expression in lung tissue were higher, by 2.04- and 2.33-fold, respectively, in CS-exposed rats than in controls ( P < 0.05). Exogenous administration of NaHS to CS-exposed rats alleviated airway reactivity induced by acetylcholine (Ach) or potassium chloride (KCl) by 17.4% and 13.8%, respectively, decreased lung pathology score by 32.7%, inhibited IL-8 and TNF- α concentrations in lung tissue by 34.2% and 31.4%, respectively, as compared with CS-exposed rats (all P < 0.05). However, blocking endogenous CSE with PPG in CS-exposed rats increased airway reactivity induced by Ach or KCl, by 24.1% and 24.5%, respectively, and aggravated lung pathology score, by 44.8%, as compared with CS-exposed rats (all P < 0.01). Incubation in vitro with NaHS, 1–3 mmol/L, relaxed rat tracheal smooth muscle precontracted by Ach or KCl. However, the NaHS-induced relaxation was not blocked by glibenclamide (10 −4 mol/L), L-NAME (10 −4 mol/L), or ODQ (1 μmol/L) or denudation of epithelium. Endogenous H 2S may have a protective role of anti-inflammation and bronchodilation in chronic CS-induced pulmonary injury.