Formation of oedema and accumulation of eosinophils in the guinea pig lung. Inhibition by inhaled beta-stimulants.
The action of the two beta-stimulants fenoterol and SOM 1122 (alpha-[[[3-(1-benzimidazolyl)-1, 1-dimethylpropyl]amino]methyl]-2-fluoro-4-hydroxybenzyl alcohol methane sulfonate) against inflammatory correlates of bronchial asthma was investigated by performing the following experiments: Passively sensitized guinea pigs were challenged by antigen aerosol under protection of mepyramine. The animal response was a 5- to 6-fold increase in the number of eosinophils in the bronchoalveolar lavage fluid after 1 or 2 days. In addition, increased microvascular permeability was elicited in guinea pig lungs after inhalation of a low concentration of histamine for 60 min. Both inflammatory reactions were inhibited by inhalation of remarkably low concentrations (0.004-0.04%) of the two beta-stimulants. These concentrations were 5 to 75 times lower than the EC50 values required for inhibition of acetylcholine-induced bronchoconstriction in the same species. The lung eosinophilia was not modified by inhibitors of lipoxygenase or cyclo-oxygenase.
Fügner
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Department of Pharmacology, Boehringer Ingelheim, FRG.
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001986:Bronchial Spasm / Q000473:pathology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects; D004487:Edema / Q000209:etiology*; D004804:Eosinophils / Q000502:physiology*; D005280:Fenoterol / Q000494:pharmacology*; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000473:pathology / Q000503:physiopathology*; D008775:Methylprednisolone / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology
D001562:Benzimidazoles; D011720:Pyrazoles; D005280:Fenoterol; C056531:SOM 1122; C015429:phenidone; D000109:Acetylcholine; D008775:Methylprednisolone; D007213:Indomethacin