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Pharmacological bronchodilation is partially mediated by reduced airway wall stiffness

Ansell, T.K.ORCID: 0000-0003-1412-762X, Noble, P.B., Mitchell, H.W. and McFawn, P.K. (2014) Pharmacological bronchodilation is partially mediated by reduced airway wall stiffness. British Journal of Pharmacology, 171 (19). pp. 4376-4384.

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Background and Purpose In asthmatic patients, airflow limitation is at least partly reversed by administration of pharmacological bronchodilators, typically β2-adrenoceptor agonists. In addition to receptor-mediated bronchodilation, the dynamic mechanical environment of the lung itself can reverse bronchoconstriction. We have now explored the possibility that bronchodilators exert a synergistic effect with oscillatory loads by virtue of reducing airway wall stiffness, and therefore, enhancing the bronchodilatory response to breathing manoeuvres. Experimental Approach Whole porcine bronchial segments in vitro were contracted to carbachol and relaxed to the non-specific β-adrenoceptor agonist, isoprenaline, under static conditions or during simulated breathing manoeuvres. Key Results The bronchodilatory response to isoprenaline was greater during breathing manoeuvres compared with the response under static conditions. As the bronchodilatory response to breathing manoeuvres is dependent upon airway smooth muscle (ASM) strain, and therefore, airway wall stiffness, our findings are likely to be explained by the effect of isoprenaline on reducing airway wall stiffness, which increased ASM strain, producing greater bronchodilation. Conclusions and Implications A contribution of reduced airway stiffness and increased ASM strain to the bronchodilator action of isoprenaline is shown, suggesting that oscillatory loads act synergistically with pharmacologically mediated bronchodilation. The implications for the treatment of asthma are that reducing airway wall stiffness represents a potential target for novel pharmacological agents.

Item Type: Journal Article
Publisher: Nature Publishing Group
Copyright: © 2014 The British Pharmacological Society.
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