TOLERANCE OF GUINEA‐PIG AIRWAY MUSCLE PREPARATIONS TO RELAXANT AGONISTS INDUCED BY CHRONIC EXPOSURE TO ISO‐PRENALINE in vivo

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Abstract
The histamine sensitivities of complete tracheal spiral preparations from guinea‐pigs were similar to those of paired half tracheal tissues. Airway muscle preparations from animals chronically treated with isoprenaline showed a significant increase in resting tone and a significant decreased responsiveness to histamine. The paired half tracheal preparations exhibited no significant difference when either their isoprenaline or theophylline sensitivities were compared. Paired half tracheal muscle preparations from chronically treated animals (0.4 μmol, 4.0 μmol, and 40.0 μmol isoprenaline, 3 times daily for 21 days, s.c.) showed a significantly reduced sensitivity to isoprenaline when compared to appropriate controls. Theophylline concentration‐effect curves for the paired half tracheal preparations from chronically treated guinea‐pigs (4.0 μmol and 40.0 μmol isoprenaline) were significantly reduced compared with appropriate controls. Indomethacin treatment reversed the isoprenaline desensitization induced by chronic treatment (0.4 μmol isoprenaline) but was ineffective in animals that received the higher doses of isoprenalinein vivo.
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