Shiozaki K, Saito Y, Sasaki F, Ishizaki T, Inui T, Yamamura T, Matsukawa S, Miyamori I
The Third Department of Internal Medicine, Fukui Medical University, Fukui, Japan.
Pulm Pharmacol Ther. 2000;13(2):79-86. doi: 10.1006/pupt.2000.0234.
Hypoxia induces bronchodilation in vivo and in vitro, but the mechanisms are still unclear. To evaluate whether an extra- or intracellular free Ca(2+) ion is involved in the mechanisms of hypoxic relaxation, we simultaneously measured cytosolic Ca(2+)levels and tensions in both intact and denuded guinea-pig tracheal strips precontracted with histamine (100 microM), and assessed the effect of hypoxia on guinea-pig tracheal rings precontracted with okadaic acid (10 microM) and calyculin-A (0.1 approximately 10 microM) under an extracellular Ca(2+)-free state. The exposure of tracheal rings to hypoxia induced an immediate decrease of tracheal tension without decrease in intracellular free Ca(2+)levels. In the presence of okadaic acid but not calyculin-A, hypoxic air exposure caused significant transient reductions in tracheal tone. Further, thapsigargin (5 microM or 10 microM) did not affect hypoxic bronchodilation, suggesting that the release of intracellular Ca(2+) does not take a role in hypoxic bronchodilation. Hypoxic dilation decreased ATP content in epithelium-intact rings but not epithelium-denuded rings, indicating a relationship between hypoxic dilation and change of adenine nucleotide in epithelium-intact rings. Our findings indicate that the epithelium dependent mechanisms of hypoxic relaxation of guinea pig tracheal rings preconstricted with histamine may not be related to the mobilization of extra and intra-cellular Ca(2+).
缺氧在体内和体外均可诱导支气管舒张，但其机制仍不清楚。为了评估细胞外或细胞内游离钙离子是否参与缺氧性舒张机制，我们同时测量了完整和去上皮的豚鼠气管条带（预先用组胺（100微摩尔）预收缩）中的胞质钙离子水平和张力，并在无细胞外钙离子状态下评估了缺氧对预先用冈田酸（10微摩尔）和花萼海绵诱癌素A（0.1至10微摩尔）预收缩的豚鼠气管环的影响。将气管环暴露于缺氧环境中可立即导致气管张力降低，而细胞内游离钙离子水平并未降低。在存在冈田酸而非花萼海绵诱癌素A的情况下，暴露于缺氧空气中会导致气管张力出现显著的短暂降低。此外，毒胡萝卜素（5微摩尔或10微摩尔）并不影响缺氧性支气管舒张，这表明细胞内钙离子的释放不参与缺氧性支气管舒张。缺氧性舒张降低了完整上皮环中的ATP含量，但未降低去上皮环中的ATP含量，这表明完整上皮环中缺氧性舒张与腺嘌呤核苷酸变化之间存在关联。我们的研究结果表明，组胺预收缩的豚鼠气管环缺氧性舒张的上皮依赖性机制可能与细胞外和细胞内钙离子的动员无关。
