Souhrada J F, Loader J
Respir Physiol. 1979 Feb;36(2):231-47. doi: 10.1016/0034-5687(79)90027-6.
This study investigated the response of isolated tracheal preparation (ITP) from guinea pigs to three bronchoconstrictive drugs: histamine (H), carbachol (CAR), and acetylcholine (ACH). Cumulative dose-response curves were obtained in substrate-rich (5.50 mM of glucose) and substrate-free physiological salt solutions under aerobic conditions (PO2 = 95 +/- 0.5 Torr) or in acute 30-min hypoxia (PO2 = 30 +/- 2 Torr). The reactivity of ITP was measured by ED50 (effective dose developing 50% of maximal response); and the contractility of ITP was measured by a maximal developed isometric tension. This study showed that the contractile response of isolated segments of tracheas to H, CAR, and ACH was significantly decreased (P less than 0.05) when the experimental medium contained no glucose, or when glucose was replaced with metabolic inhibitor 2-deoxyglucose. This data contrasted with findings obtained with main pulmonary arteries (MPAs) isolated from the same species, where the absence of glucose in the experimental medium did not affect patterns of histamine cumulative dose-response curves. It was also shown that pretreatment of isolated tracheas with a small dose of insulin significantly decreased (P less than 0.05) the contractile response of airway smooth muscle to histamine. In both experiments, either with or without glucose in the experimental medium, acute hypoxia (30 min) had a significantly greater effect (P less than 0.05) on the development of isometric tension of MPA compared with that on ITP. Both removal of glucose from the experimental medium and/or acute hypoxia significantly decreased (P less than 0.001) adenosin triphosphate and creatine phosphate contents of tracheal segments but did not influence the high-energy phosphate content of main pulmonary arteries exposed to similar conditions. In addition to pointing out the physiological and metabolic differences between pulmonary vascular and airway smooth muscle, this study showed the important dependence of airway smooth muscle on glucose as a substrate.
本研究调查了豚鼠离体气管制备物（ITP）对三种支气管收缩药物的反应：组胺（H）、卡巴胆碱（CAR）和乙酰胆碱（ACH）。在富含底物（5.50 mM葡萄糖）和无底物的生理盐溶液中，于有氧条件（PO2 = 95±0.5 Torr）或急性30分钟缺氧（PO2 = 30±2 Torr）下获得累积剂量反应曲线。ITP的反应性通过ED50（产生最大反应50%的有效剂量）来测量；ITP的收缩性通过最大等长张力来测量。本研究表明，当实验培养基不含葡萄糖或用代谢抑制剂2-脱氧葡萄糖替代葡萄糖时，气管离体节段对H、CAR和ACH的收缩反应显著降低（P<0.05）。该数据与从同一物种分离的主肺动脉（MPA）的研究结果形成对比，在主肺动脉的实验中，实验培养基中缺乏葡萄糖并不影响组胺累积剂量反应曲线的模式。还表明，用小剂量胰岛素预处理离体气管可显著降低（P<0.05）气道平滑肌对组胺的收缩反应。在这两个实验中，无论实验培养基中有无葡萄糖，急性缺氧（30分钟）对MPA等长张力发展的影响均显著大于对ITP的影响（P<0.05）。从实验培养基中去除葡萄糖和/或急性缺氧均显著降低（P<0.001）气管节段的三磷酸腺苷和磷酸肌酸含量，但不影响暴露于类似条件下的主肺动脉的高能磷酸含量。除了指出肺血管和平滑肌之间的生理和代谢差异外，本研究还表明气道平滑肌对葡萄糖作为底物的重要依赖性。
