Small airways are a major site of airflow limitation in chronic obstructive pulmonary disease (COPD). Despite the detrimental effects of long-term smoking in COPD, the effects of acute cigarette smoke exposure on small airway reactivity have not been fully elucidated. Balb/C mice were exposed to room air (sham) or cigarette smoke for 4 days to cause airway inflammation. Changes in small airway lumen area in response to contractile agents were measured in lung slices in situ using phase-contrast microscopy. Separate slices were pharmacologically maintained at constant intracellular Ca2+ using caffeine/ryanodine prior to contractile measurements. Gene and protein analysis of contractile signaling pathways were performed on separate lungs. Monophasic contraction to serotonin became biphasic after cigarette smoke exposure, while contraction to methacholine was unaltered. This altered pattern of contraction was normalised by caffeine/ryanodine. Expression of contractile agonist-specific receptors was unaltered, however all isoforms of the ryanodine receptor were down regulated. This is the first study to show that acute cigarette smoke exposure selectively alters small airway contraction to serotonin and down-regulates ryanodine receptors involved in maintaining Ca2+-oscillations in airway smooth muscle. Understanding the contribution of ryanodine receptors to altered airway reactivity may inform the development of novel treatment strategies for COPD.
|Pages (from-to)||471 - 478|
|Number of pages||8|
|Journal||American Journal of Respiratory Cell and Molecular Biology|
|Publication status||Published - 2015|