The Effect of Oxygen Tension on Responses Evoked by Methacholine and Bronchodilators in Bovine Isolated Bronchial Rings

Abstract

This study examined the effect of acute changes in oxygen tension on responses evoked by the bronchoconstrictor methacholine and the dilators salbutamol, atrial natriuretic peptide and isosorbide dinitrate in isolated bovine bronchi. Cumulative concentration–response curves to methacholine (10⁻⁹–3×10⁻⁴M) were constructed in three oxygen tensions; hyperoxia (95%), normoxia (20%) and hypoxia (4% O₂). Oxygen tensions of 20% and 4% each significantly enhanced contractions to methacholine compared to those in 95% O₂. There was no significant difference, however, between responses in 20 and 4%. The ability of salbutamol, atrial natriuretic peptide and isosorbide dinitrate to reverse methacholine induced tone was also compared in the three oxygen tensions (95%, 20% and 4%). Lowering the oxygen tension from 95% enhanced the ability of each of the drugs to reverse contraction, however the pattern differed between drugs; salbutamol was more effective in 20% O₂than 4%, atrial natriuretic peptide was more effective in 4% than either 95 or 20% O₂and isosorbide dinitrate was more effective in both 4 and 20% than 95% O₂. In conclusion, both bronchoconstrictor and bronchodilator responses in 95% O₂(hyperoxia) differed from those in 20% O₂(normoxia) and further changes occurred on moving to 4% (hypoxia), although the direction of the changes varied among the dilators. This suggests that the responses evoked by bronchodilators in 95% O₂may not necessarily predict those in the physiological range of oxygen tensions and that the relative effectiveness of bronchodilators may vary between normoxic and hypoxic conditions.