[The inhibiting effect of niflumic acid on airway hyperresponsiveness in asthmatic mice].
OBJECTIVE
To evaluate the inhibiting effect of niflumic acid (NFA), an inhibitor of calcium-activated chloride channel (ClCa) on airway epithelium, on the airway hyperresponsiveness in asthmatic mice.


METHODS
BALB/c mice were randomly divided into an asthma group (A group), a NFA prevention asthmatic group (B group) and a sham-challenged group (C group). The airway pressure time index (APTI) and the content of ET-1 and NO in bronchoalveolar lavage fluid (BALF) in all groups were measured. With the isolated tracheal rings with integral epithelium or epithelium removed from the asthma group (A(1) group and A(2) group) and the sham-challenged group (C(1) group and C(2) group), the contractile responsiveness of various rings to methacholine (mACh) was examined, and its change was observed when the rings were exposed to NFA beforehand.


RESULTS
Compared with A group (1.62 +/- 0.14), the APTI in B group (1.21 +/- 0.07) was reduced remarkably (P < 0.01), and the contents of ET-1 [(103 +/- 9) ng/L] and NO [(48.5 +/- 3.2) micromol/L] in BALF of A group were significantly higher than those in B group, [(53 +/- 5) ng/L, (23.7 +/- 2.5) micromol/L (P < 0.01), respectively]. The ratios of maximum contractility in A(1), A(2), C(1) and C(2) groups were (3.79 +/- 0.44), (2.15 +/- 0.21), (1.26 +/- 0.14) and (2.06 +/- 0.18), respectively. The contractility of A(1) group was highest among all groups (all P < 0.01), but could be effectively decreased by NFA.


CONCLUSIONS
By inhibiting the special ClCa on the airway epithelium, NFA can inhibit the production of ET-1 and NO by epithelium and thus exert preventive effect on airway hyperresponsiveness in asthma.
Department of Respiratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an 710033, China.
Li-qiang
LQ
Song
Yan
Y
Li
Le-ning
LN
Zhang
Fang
F
Gao
Jiu-hua
JH
Cheng
Hao-wen
HW
Qi
D000818:Animals; D001249:Asthma / Q000188:drug therapy*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D019332:Endothelin-1 / Q000032:analysis; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009544:Niflumic Acid / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000032:analysis; D014132:Trachea / Q000187:drug effects
D019332:Endothelin-1; D009569:Nitric Oxide; D009544:Niflumic Acid