Abstract
Hypoxia induces bronchodilation in vivo and in vitro, but the mechanisms are still unclear. To evaluate whether an extra- or intracellular free Ca2+ion is involved in the mechanisms of hypoxic relaxation, we simultaneously measured cytosolic Ca2+levels and tensions in both intact and denuded guinea-pig tracheal strips precontracted with histamine (100 μM), and assessed the effect of hypoxia on guinea-pig tracheal rings precontracted with okadaic acid (10 μM) and calyculin-A (0.1≈10 μM) under an extracellular Ca2+-free state. The exposure of tracheal rings to hypoxia induced an immediate decrease of tracheal tension without decrease in intracellular free Ca2+levels. In the presence of okadaic acid but not calyculin-A, hypoxic air exposure caused significant transient reductions in tracheal tone. Further, thapsigargin (5 μM or 10 μM) did not affect hypoxic bronchodilation, suggesting that the release of intracellular Ca2+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 Ca2+.
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