[Role of peroxynitrite on airway hyperresponsiveness in asthmatic guinea-pigs].
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.


CONCLUSIONS
There was ONOO- overproduction in airway epithelial cells of asthmatic guinea-pigs, which may contribute to airway epithelial damage and hyperresponsiveness in asthma.
Zhu
T
T
Department of Pathophysiology, Hebei Medical University, Shijiazhuang 050017, China.
Ling
Y
Y
Zhao
R
R
D000818:Animals; D001249:Asthma / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D006168:Guinea Pigs; D007150:Immunohistochemistry; D008297:Male; D030421:Peroxynitrous Acid / Q000378:metabolism*
D030421:Peroxynitrous Acid