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[Role of peroxynitrite on airway hyperresponsiveness in asthmatic guinea-pigs]
1Department of Pathophysiology, Hebei Medical University, Shijiazhuang 050017, China.
Objective:
To study the formation and localization of peroxynitrite(ONOO-) in the lung tissues of asthmatic guinea pig and investigate the effects of ONOO- on airway hyperresponsiveness in asthma.
Methods:
18 guinea pigs were randomly divided into three groups of 6 each: (1) asthmatic group: guinea pigs were injected intraperitoneally with 1 ml of 10% ovalbumin. After 14 days, the animals were exposed to aerosol of 1% OVA; (2) aminoguonidine (AG) group: Animal immunization was the same as above, but 1 h before the animals were exposed to OVA aerosol, 10 mg/kg AG were injected intraperitoneally. (3) control group. The formation and localization of ONOO- in the lung tissues of the guinea-pig asthma model were observed by immunohistochemical detection. The effect of exogenous ONOO- on contractions of isolated tracheal strips of the guinea-pigs to various concentrations of histamine was examined. The damage of airway epithelial cells induced by ONOO- was observed by electron microscopy.
Results:
There was strong immunoreactivity for nitrotyrosine (NT), a specific marker of ONOO- formation in vivo, in the airway epithelial cells and inflammatory cells surrounding small airways of the guinea-pigs with asthma. The AG group showed significantly decreased number of NT positive cells in the lung tissues. There were only a few NT positive cells in the control group. The responsiveness of isolated tracheal strips to various concentration of histamine(except 10(-8) mol/L) in the ONOO- 0.5 mmol/L group were significantly increased compared with the vehicle group. (P < 0.05, P < 0.01 or P < 0.001). The sensitivity of isolated tracheal strips to histamine in the ONOO- 0.5 mmol/L group were also increased compared with the vehicle group(P < 0.001). Electron microscopical observation of the airways revealed airway epithelial injury and shedding.
Conclusion:
There was ONOO- overproduction in airway epithelial cells of asthmatic guinea-pigs, which may contribute to airway epithelial damage and hyperresponsiveness in asthma.