Effects of β-blockers on house dust mite-driven murine models pre- and post-development of an asthma phenotype.

Background: Our previous studies suggested certain beta-adrenoceptor blockers (beta-blockers) attenuate the asthma phenotype in ovalbumin driven murine models of asthma. However, the ovalbumin model has been criticized for lack of clinical relevance. Methods: We tested the non-selective beta-blockers, carvedilol and nadolol, in house dust mite (HDM) driven murine asthma models where drugs were administered both pre- and post-development of the asthma phenotype. We measured inflammation, mucous metaplasia, and airway hyper-responsiveness (AHR). We also measured the effects of the beta-blockers on extracellular-signal regulated kinase (ERIC 1/2) phosphorylation in lung homogenates. Results: We show that nadolol, but not carvedilol, attenuated inflammation and mucous metaplasia, and had a moderate effect attenuating AHR. Following HDM exposure, ERR1/2 phosphorylation was elevated, but the level of phosphorylation was unaffected by beta-blockers, suggesting ERK1/2 phosphorylation becomes dissociated from the asthma phenotype. Conclusion: Our findings in HDM models administering drugs both pre- and post-development of the asthma phenotype are consistent with previous results using ovalbumin models and show differential effects for nadolol and carvedilol on the asthma phenotype. Lastly, our data suggest that ERK1/2 phosphorylation may be involved in development of the asthma phenotype, but may have a limited role in maintaining the phenotype. (C) 2017 Elsevier Ltd. All rights reserved.