Clayton R A, Nally J E, Thomson N C, McGrath J C
Division of Neuroscience and Biomedical Systems, University of Glasgow, Scotland.
Pulm Pharmacol. 1996 Apr;9(2):123-8. doi: 10.1006/pulp.1996.0014.
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 x 10(-4) M) 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% O2 than 4%, atrial natriuretic peptide was more effective in 4% than either 95 or 20% O2 and 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% O2 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.
本研究检测了氧分压急性变化对离体牛支气管中支气管收缩剂乙酰甲胆碱以及支气管扩张剂沙丁胺醇、心房利钠肽和硝酸异山梨酯所诱发反应的影响。在三种氧分压条件下构建了对乙酰甲胆碱（10⁻⁹ - 3×10⁻⁴ M）的累积浓度-反应曲线，分别为高氧（95%）、常氧（20%）和低氧（4% O₂）。与95% O₂相比，20%和4%的氧分压均显著增强了对乙酰甲胆碱的收缩反应。然而，20%和4%条件下的反应之间没有显著差异。还比较了在三种氧分压（95%、20%和4%）下沙丁胺醇、心房利钠肽和硝酸异山梨酯逆转乙酰甲胆碱诱导张力的能力。将氧分压从95%降低增强了每种药物逆转收缩的能力，然而不同药物的模式有所不同；沙丁胺醇在20% O₂中比在4%时更有效，心房利钠肽在4%时比在95%或20% O₂时更有效，硝酸异山梨酯在4%和20%时比在95% O₂时更有效。总之，95% O₂（高氧）中的支气管收缩和扩张反应与20% O₂（常氧）中的不同，并且在降至4%（低氧）时进一步发生变化，尽管不同扩张剂的变化方向有所不同。这表明95% O₂中支气管扩张剂诱发的反应不一定能预测在生理氧分压范围内的反应，并且支气管扩张剂的相对有效性在常氧和低氧条件下可能会有所不同。
