Tolerance of guinea-pig airway muscle preparations to relaxant agonists induced by chronic exposure to isoprenaline in vivo.

1 The histamine sensitivities of complete tracheal spiral preparations from guinea-pigs were similar to those of paired half tracheal tissues. 2 Airway muscle preparations from animals chronically treated with isoprenaline showed a significant increase in resting tone and a significant decreased responsiveness to histamine. 3 The paired half tracheal preparations exhibited no significant difference when either their isoprenaline or theophylline sensitivities were compared. 4 Paired half tracheal muscle preparations from chronically treated animals (0.4 mumol, 4.0 mumol, and 40.0 mumol isoprenaline, 3 times daily for 21 days, s.c.) showed a significantly reduced sensitivity to isoprenaline when compared to appropriate controls. 5 Theophylline concentration-effect curves for the paired half tracheal preparations from chronically treated guinea-pigs (4.0 mumol and 40.0 mumol isoprenaline) were significantly reduced compared with appropriate controls. 5 Indomethacin treatment reversed the isoprenaline desensitization induced by chronic treatment (0.4 mumol isoprenaline) but was ineffective in animals that received the higher doses of isoprenaline in vivo.