title: Involvement of endogenous hydrogen sulfide in cigarette smoke-induced changes in airway responsiveness and inflammation of rat lung.
abstract: Hydrogen sulfide (H₂S), recently considered the third endogenous gaseous transmitter, may have an important role in systemic inflammation. We investigated whether endogenous H₂S 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 H₂S) or propargylglycine (PPG, inhibitor of cystathionine-γ-lyase [CSE], an H₂S-synthesizing enzyme) for 4-month exposure. Serum H₂S 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 H₂S may have a protective role of anti-inflammation and bronchodilation in chronic CS-induced pulmonary injury.
authors.affiliation: Respiratory Department, Peking University Third Hospital, Beijing 100191, China. chenyahong@vip.sina.com
authors.forename: Ya-Hong
authors.initials: YH
authors.lastname: Chen
authors.forename: Pei-Pei
authors.initials: PP
authors.lastname: Wang
authors.forename: Xin-Mao
authors.initials: XM
authors.lastname: Wang
authors.forename: Yan-Jing
authors.initials: YJ
authors.lastname: He
authors.forename: Wan-Zhen
authors.initials: WZ
authors.lastname: Yao
authors.forename: Yong-Fen
authors.initials: YF
authors.lastname: Qi
authors.forename: Chao-Shu
authors.initials: CS
authors.lastname: Tang
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000480:Alkynes / Q000494:pharmacology; D000818:Animals; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000097:blood* / Q000378:metabolism; D066298:In Vitro Techniques; D007249:Inflammation / Q000097:blood* / Q000209:etiology; D016209:Interleukin-8 / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012130:Respiratory Hypersensitivity / Q000097:blood* / Q000209:etiology; D012906:Smoke / Q000009:adverse effects*; D013440:Sulfides / Q000494:pharmacology; D014026:Nicotiana / Q000737:chemistry; D014132:Trachea / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000480:Alkynes; D016209:Interleukin-8; D012906:Smoke; D013440:Sulfides; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; C009055:propargylglycine; D003542:Cystathionine gamma-Lyase; C025451:sodium bisulfide; D000109:Acetylcholine; D005998:Glycine; D006862:Hydrogen Sulfide