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

• Published in: Pulmonary pharmacology & therapeutics 2017-10, Vol.46, p.30-40
• Main Authors: Joshi, Radhika, Valdez, Daniel, Kim, Hosu, Eikenburg, Douglas C., Knoll, Brian J., Bond, Richard A.
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Antagonists - pharmacology; Animals; Asthma; Asthma - drug therapy; Asthma - immunology; Asthma - pathology; Carbazoles - pharmacology; Disease Models, Animal; Extracellular-signal regulated kinases 1/2; House dust mite; Inflammation - drug therapy; Inflammation - pathology; Male; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Murine model; Nadolol - pharmacology; Ovalbumin - immunology; Phenotype; Phosphorylation; Propanolamines - pharmacology; Pyroglyphidae - immunology; Respiratory Hypersensitivity - drug therapy; β-adrenoceptor blockers
• ISSN: 1094-5539; 1522-9629
• DOI: 10.1016/j.pupt.2017.07.004

Our previous studies suggested certain β-adrenoceptor blockers (β-blockers) attenuate the asthma phenotype in ovalbumin driven murine models of asthma. However, the ovalbumin model has been criticized for lack of clinical relevance. We tested the non-selective β-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 β-blockers on extracellular-signal regulated kinase (ERK 1/2) phosphorylation in lung homogenates. We show that nadolol, but not carvedilol, attenuated inflammation and mucous metaplasia, and had a moderate effect attenuating AHR. Following HDM exposure, ERK1/2 phosphorylation was elevated, but the level of phosphorylation was unaffected by β-blockers, suggesting ERK1/2 phosphorylation becomes dissociated from the asthma phenotype. 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.