Intrinsic tone in human airway smooth muscle increases subsequent contractile response

Introduction: Small airway abnormalities are implicated as a primary cause of functional impairment in obstructive airway disease. Contraction of the airway smooth muscle (ASM) layer in the absence of an exogenous stimulus (i.e. intrinsic tone) may enhance force production through ‘force adaptation’. This study determined the relationship between intrinsic ASM tone and subsequent response to contractile activation. Methods: Subjects (n=18) undergoing lobectomies were recruited and baseline lung function assessed before surgery. Peripheral airways were dissected from resected tissue and cut into bronchial rings for further in vitro studies. Length-force curves were constructed to KCl to establish optimum contractile length, at which dose-response curves to acetylcholine (ACh) were performed. Intrinsic force was determined after complete relaxation to theophylline. Forces were converted to stress after normalising for muscle thickness and ring width. Data are mean±SEM. Results: Subjects had a pre-bronchodilator FEV1(%Pred) of 93±3.91 and FEV1/FVC of 0.73±0.02. Bronchial rings exhibited a mean intrinsic stress of 29±5.14mN/mm2 which comprised ~28% of the total (intrinsic + active) stress. Intrinsic stress was positively correlated with maximal response to ACh (r=0.55, p<0.05) but not sensitivity. There was no association between lung function and intrinsic ASM stress or maximal stress induced by ACh. Conclusion: Results demonstrate that increased intrinsic tone in the peripheral ASM layer increases the subsequent response of the airway to contractile activation. This suggests that elevated intrinsic tone may increase induced bronchoconstriction to inhaled stimuli and promote airway hyperresponsiveness.