The Effects of Lipopolysaccharide on the Reactivity of Isolated Rat Trachea with or without Epithelium

Shin, Hyo Chul; Kim, Yoon Hee; Hur, Dong Sik; Yoon, Seok Hwa; Shin, Yong Sup; Choi, Sae Jin

Abstract

BACKGOUND: Gram negative bacterial lipopolysaccharide (LPS) induces increase in the production of nitric oxide (NO), or a related substance derived from L-arginine in the animal tissue. Recent evidence indicates that airway epithelium may secrete NO or a related compound. It has multiple regulatory roles in the airways. In vitro, the effects of lipopolysaccharide (LPS) on the reactivity of rat' tracheal wall with or without epithelium were examined.
METHODS
Tracheas were removed from Sprague Dawley rats. Preparations were mounted for isometric recording in 20ml organ baths at 37degrees C containing Tis-buffered Tyrode solution continuously gassed with 100% O2. Tensions were measured with force displacement transducers and responses were recorded on a polygraph. Cummulative concentration-response curves were constructed for acetylcholine (Ach) in the tracheal strips with or without preincubation of Escherichia coli LPS (100 mcg/ml, 5hrs). And then effects of NO synthase inhibitors and removal of epithelium were examined.
RESULTS
In isolated perfused tracheas preincubated by LPS, both removed epithelium and intact epithelium of rat tracheal rings showed decreased Ach-induced contraction. In intact epithelium group, 10 (-5)M L-NAME (N-nitro-L-arginine methyl ester), 10 (-5)M L-arginine or dexamethasone pretreatment was restored in Ach-induced contraction response. But in the removed epithelium group, Ach-induced contraction was potentiated by L-arginine pretreatment and was not restored by the pretreatment of L-NAME and dexamethasone.
CONCLUSIONS
The results suggest that nitric oxide synthase is induced by endotoxin in the tracheal epithelium, resulting in inhibition of the contractile response.