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Impaired Bronchoprotection Is Not Induced by Increased Smooth Muscle Mass in Chronic Treatment In Vivo with Formoterol in Asthmatic Mouse Model



Objective: Inhaling β2-adrenoceptor agonist is first-line asthma treatment, which is used for both acute relief and prevention of bronchoconstriction. However, chronic use of β-agonists results in impaired bronchoprotection and increasing occurrences of severe asthma exacerbation, even death in clinical practice. The mechanism of β-adrenoceptor hyposensitivity has not been thoroughly elucidated thus far. Bronchial smooth muscle contraction induces airway narrowing and also mediates airway inflammation. Moreover, bronchial smooth muscle mass significantly increases in asthmatics. We aimed to establish an asthmatic model that demonstrated that formoterol induced impaired bronchoprotection and to see whether increased smooth muscle mass played a role in it.

Methods: We combined routine allergen challenging (seven weeks) with repeated application of formoterol, formoterol plus budesonide or physiological saline in allergen-sensitized BALB/c mouse. The bronchoprotection mediated by β-agonist was measured in five consecutive weeks. Smooth muscle mass was shown by morphometric analysis, and α-actin expression was detected by western blot.

Results: The trend of bronchoprotection was wavy in drug interventional groups, which initially increased and then decreased. Chronic treatment with formoterol significantly impaired bronchoprotection. According to the morphometric analysis and α-actin expression, no significant difference was detected in smooth muscle mass in all groups.

Conclusion: This experiment successfully established that a chronic asthmatic mouse model, which manifested typical features of asthmatic patients, when treated chronically with formoterol, showed a loss of bronchoprotection. No significant difference was detected in smooth muscle mass in all groups, which implied some subcellular signalling changes may be the key points.  

**Previously published in WIMJ Open 2014; 1 (3) 
11 Aug, 2014
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e-Published: 16 Jan, 2015
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