Roles of oxygen radicals and elastase in citric acid-induced airway constriction of guinea-pigs.
Antioxidants attenuate noncholinergic airway constriction. To further investigate the relationship between tachykinin-mediated airway constriction and oxygen radicals, we explored citric acid-induced bronchial constriction in 48 young Hartley strain guinea-pigs, divided into six groups: control; citric acid; hexa(sulphobutyl)fullerenes + citric acid; hexa(sulphobutyl)fullerenes + phosphoramidon + citric acid; dimethylthiourea (DMTU) + citric acid; and DMTU + phosphoramidon + citric acid. Hexa(sulphobutyl)fullerenes and DMTU are scavengers of oxygen radicals while phosphoramidon is an inhibitor of the major degradation enzyme for tachykinins. Animals were anaesthetized, paralyzed, and artificially ventilated. Each animal was given 50 breaths of 4 ml saline or citric acid aerosol. We measured dynamic respiratory compliance (Crs), forced expiratory volume in 0.1 (FEV0.1), and maximal expiratory flow at 30% total lung capacity (Vmax30) to evaluate the degree of airway constriction. Citric acid, but not saline, aerosol inhalation caused marked decreases in Crs, FEV0.1 and Vmax30, indicating marked airway constriction. This constriction was significantly attenuated by either hexa(sulphobutyl)fullerenes or by DMTU. In addition, phosphoramidon significantly reversed the attenuating action of hexa(sulphobutyl)fullerenes, but not that of DMTU. Citric acid aerosol inhalation caused increases in both lucigenin- and t-butyl hydroperoxide-initiated chemiluminescence counts, indicating citric acid-induced increase in oxygen radicals and decrease in antioxidants in bronchoalveolar lavage fluid. These alterations were significantly suppressed by either hexa(sulphobutyl)fullerenes or DMTU. An elastase inhibitor eglin-c also significantly attenuated citric acid-induced airway constriction, indicating the contributing role of elastase in this type of constriction. We conclude that both oxygen radicals and elastase play an important role in tachykinin-mediated, citric acid-induced airway constriction.
Lai
Y L
YL
Department of Physiology, College of Medicine, National Taiwan University, Taipei, ROC. tiger@ha.mc.ntu.edu.tw
Chiou
W Y
WY
Lu
F J
FJ
Chiang
L Y
LY
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid; D016084:Bronchoconstriction / Q000187:drug effects*; D002614:Chelating Agents / Q000494:pharmacology*; D019343:Citric Acid / Q000494:pharmacology*; D005541:Forced Expiratory Volume / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D006168:Guinea Pigs; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000502:physiology*; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D011506:Proteins; D017382:Reactive Oxygen Species / Q000502:physiology*; D012129:Respiratory Function Tests; D015843:Serpins / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014797:Vital Capacity / Q000187:drug effects; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D002614:Chelating Agents; D016166:Free Radical Scavengers; D011506:Proteins; D017382:Reactive Oxygen Species; D015843:Serpins; C028656:eglin proteinase inhibitors; D019343:Citric Acid; C038983:1,3-dimethylthiourea; D020122:tert-Butylhydroperoxide; D010196:Pancreatic Elastase; D013890:Thiourea