[The role of endogenous nitric oxide in airway hyperresponsiveness of asthmatic rats].
OBJECTIVE
Nitric oxide (NO) precursor L-arginine (L-Arg) and NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) were used to investigate the role of endogenous NO in airway hyperresponsiveness of asthmatic rats.


METHODS
Asthmatic wistar rats were developed by sensitization and challenging with ovalbumin. Airway responsivess to acetylcholine (Ach) was measured in vitro in isolated and perfused rat tracheal rings with or without epithelium after inhibiting or stimulating NO synthesis.


RESULTS
After asthmatic rat tracheal rings were incubated in vitro with L-NAME 10(-5) mol/L, the maximal response of tracheal rings to Ach was increased compared with that of the control group. When asthmatic rat tracheal rings were coincubated with L-Arginine 2 x 10(-5) mol/L and L-NAME 10(-5) mol/L, the maximal response was decreased compared with that of the L-NAME group. Incubation with higher concentrations of L-Arginine did not change asthmatic rat tracheal responsiveness to Ach. Epithelium-denuded tracheal rings in the asthmatic rats showed a significant (P < 0.05) upward shift in the Ach concentration response curve; the maximal response was increased compared with the tracheal intact group. In the denuded tracheal rings, L-NAME and L-Arginine did not influence the shape of the Ach concentration-response curve and the maximal response.


CONCLUSIONS
Endogenous nitric oxide, a mediator of bronchodilation, is synthesized from L-Arginine by NO synthase in asthmatic rats. The epithelium lining airway smooth muscle probably contributes to nitric oxide synthesis. Our finding suggests that the airway in asthmatic rats could not use exogenous L-Arginine to synthesize nitric oxide.
Huang
T
T
Department of Respiratory Diseases, Peking Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730.
Lin
Y
Y
Zhu
Y
Y
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001249:Asthma / Q000503:physiopathology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors; D006967:Hypersensitivity / Q000209:etiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester