Abstract
Purpose
Gradually progressing contraction of airway smooth muscle is suggested to be due to the Rho-kinase signaling pathway. In our preliminary study in rat tracheas, landiolol, a β1-adrenoceptor antagonist, at high doses caused gradually progressing contraction, and this contraction reached a plateau after 20 min. Therefore, this study was carried out to clarify whether landiolol could stimulate the Rho-kinase pathway or the phosphatidylinositol (PI) response in the rat trachea.
Methods
Seventy-eight male Wistar rats weighing 250–350 g were used for the experiments. Their tracheas were cut into 3-mm-wide ring segments or 1-mm-wide slices. Measurements of isometric tension and [3H] inositol monophosphate (IP1) production were conducted, using these tracheal rings or slices. Data values are expressed as means ± SD, and statistical significance (P < 0.05) was determined using analysis of variance (ANOVA).
Results
Landiolol (700 μM)-induced contraction was completely inhibited by fasudil at 30 μM, while the landiolol-induced contraction was not inhibited by 4-diphenylacetoxy-N-methyl-piperidine methobromide (4-DAMP), ketanserin, or nicardipine. Landiolol did not stimulate IP1 production.
Conclusion
These results suggest that high concentrations of landiolol could cause airway smooth muscle contraction through the Rho-kinase pathway, but not through the PI response coupled with muscarinic M3 receptors, 5-HT receptors or the activation of L-type Ca2+ channels.
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Shibata, O., Nishioka, K., Yamaguchi, M. et al. High concentrations of landiolol, a β1-adrenoceptor antagonist, stimulate smooth muscle contraction of the rat trachea through the Rho-kinase pathway. J Anesth 22, 21–26 (2008). https://doi.org/10.1007/s00540-007-0567-1
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DOI: https://doi.org/10.1007/s00540-007-0567-1