Effects of lipopolysaccharide from Pseudomonas aeruginosa on airway smooth muscle functions in guinea pigs.
To elucidate the mechanisms of airway hyperreactivity induced by lipopolysaccharide (LPS), we studied isolated tracheal segments from guinea pigs under isometric conditions in vitro. Guinea pigs were injected intraperitoneally with endotoxin (1 mg/kg; LPS from Pseudomonas aeruginosa, serotype 10) for 4 days, and animals treated with sterile nonpyrogenic saline served as controls. Histological examination of trachea revealed moderate structural damage of epithelial layer in the LPS-treated group. Treatment with LPS potentiated the contractile responses of tracheal smooth muscle to acetylcholine, causing a leftward displacement of dose-response curves so that the EC50 values decreased from 1.1 +/- 3.7 x 10(-5) to 4.4 +/- 3.7 x 10(-7) M (mean +/- SE, p less than 0.01). Likewise, LPS shifted the dose-response curves for histamine and substance P to lower concentrations by approximately 0.5-1.0 log U. Each of these potentiations was not affected by pretreatment of tissues with indomethacin or propranolol. Addition of isoproterenol to tracheal segments precontracted with acetylcholine caused concentration-dependent relaxation, an effect that was significantly greater in controls than in the LPS-treated group. These results suggest that airway hyperreactivity induced by LPS in guinea pigs may be attributed to a decreased ability of respiratory epithelial cells to generate a relaxing factor.
Yamawaki
I
I
First Department of Medicine, Tokyo Women's Medical College, Japan.
Tamaoki
J
J
Kanemura
T
T
Horii
S
S
Takizawa
T
T
D000818:Animals; D001685:Biological Factors / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology; D006168:Guinea Pigs; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D014132:Trachea / Q000502:physiology*
D001685:Biological Factors; D004731:Endotoxins; D008070:Lipopolysaccharides; C056250:epithelium-derived relaxant factor