Pharmacological study of bacterial lipopolysaccharide-induced airway hyperresponsiveness in guinea-pigs.
Bacterial lipopolysaccharide-induced airway hyperreactivity in guinea-pigs was investigated pharmacologically. Inhalation of bacterial lipopolysaccharide resulted in an increase in airway muscarinic reactivity, as measured by intravenous acetylcholine administration. Metopirone, an inhibitor of 11 beta-hydroxylase, increased the excretion of urinary 17-ketosteroid, displayed a tendency to lower plasma cortisone levels and increased lipopolysaccharide-induced bronchial hyperreactivity. After bacterial lipopolysaccharide was inhaled by metopirone-treated guinea-pigs, increased vascular permeability and an increased number of leukocytes in the pulmonary capillaries were observed. When prednisolone, alone or in combination with cyclophosphamide, was injected into the guinea-pigs, lipopolysaccharide-induced airway hyperreactivity was inhibited, along with the simultaneous disappearance of inflammatory signs in the airway. Tranilast and ketotifen, reported in clinical studies to inhibit airway hyperreactivity, inhibited hyperreactivity induced by lipopolysaccharide and increased vascular permeability in the pulmonary capillaries, without affecting the increase in leukocytes. These results indicate that increased permeability in pulmonary capillaries is an important factor in the induction of lipopolysaccharide-induced bronchial hyperreactivity in guinea-pigs, and that this model is useful for the pharmacological study of airway hyperreactivity.
Nagai
H
H
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Tsuji
F
F
Goto
S
S
Koda
A
A
D015068:17-Ketosteroids / Q000652:urine; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D002199:Capillary Permeability / Q000187:drug effects; D003348:Cortisone / Q000097:blood; D003520:Cyclophosphamide / Q000494:pharmacology; D006168:Guinea Pigs; D007665:Ketotifen / Q000494:pharmacology; D007958:Leukocyte Count / Q000187:drug effects; D008070:Lipopolysaccharides; D008168:Lung / Q000098:blood supply / Q000187:drug effects; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D011239:Prednisolone / Q000494:pharmacology; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D015068:17-Ketosteroids; D008070:Lipopolysaccharides; D062367:ortho-Aminobenzoates; D003520:Cyclophosphamide; D011239:Prednisolone; C012293:tranilast; D000109:Acetylcholine; D003348:Cortisone; D007665:Ketotifen; D008797:Metyrapone