Changing the oxygen tension alters the ability of bronchodilators to protect against methacholine-induced challenge in bovine isolated bronchial rings

The ability of atrial natriuretic peptide, salbutamol, sodium nitroprusside and isosorbide dinitrate to protect against challenge with methacholine in bovine isolated bronchi was compared in different O-2 tensions. Perfusing the Krebs-Henseleit solution with gas mixtures containing 95% O-2 (hyperoxia), 20% O-2 (approximately normoxia) and 0% O-2 (hypoxia) produced O-2 tensions in the organ-baths of 524, 147 and 26 mm Hg, respectively. In hyperoxia, pre-incubation of atrial natriuretic peptide at concentrations of 3 x 10(-7)M and 10(-6)M significantly attenuated responses to methacholine, whereas in normoxia, these concentrations of atrial natriuretic peptide had no effect. Furthermore, in hypoxia, 3 x 10(-7) M and 10(-6) M atrial natriuretic peptide significantly enhanced responses to methacholine. Salbutamol, at concentrations of 3 x 10(-7) M and 10(-6) M significantly attenuated responses to methacholine in hyperoxia, whereas in normoxia and hypoxia, pre-incubation of salbutamol did not alter the methacholine response. Pre-incubation of 10(-5) M sodium nitroprusside significantly attenuated methacholine-induced contractions in hyperoxia and when the oxygen tension in the gas mixture was lowered to 20% or 0%, the ability of sodium nitroprusside to protect against methacholine challenge was enhanced. In hyperoxia, isosorbide dinitrate, at the 10(-4) M level, evoked a rightward shift of the methacholine response curve. Lowering the oxygen tension to either 20% or 0% enhanced the protectant effect of isosorbide dinitrate, with the effect being greater in 20% O-2. Thus, the effect of these bronchodilators on methacholine-induced challenge in hyperoxia O-2 differed from those in normoxia and hypoxia, although the direction of the changes varied among the agents used. This suggests that the responses evoked by bronchodilators in 95% O-2 may 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. (C) 1997 Academic Press Limited.