Description:
Asthma is characterized by chronic airway inflammation, excess mucus production and airway hyper responsiveness (AHR). Our previous research suggested that some β2‐adrenoceptor (β2AR) blockers might be beneficial in chronic asthma therapy. Using an ovalbumin (Ova) allergen‐driven murine asthma model, we have previously shown that only certain β2AR blockers such as nadolol and ICI‐118, 551 attenuate the development of an asthma phenotype when administered prior to the antigen challenge (‘prophylactic’ effect); while others including carvedilol and propranolol are ineffective. Recently however, the Ova model has been criticized for its lack of clinical relevance. To address the limitations of this model, we tested the β2AR blockers, nadolol and carvedilol in a clinically more relevant model utilizing house dust mite (HDM) extract. Additionally, we investigated both the ‘prophylactic’ and ‘therapeutic’ (the drugs were administered after the development of asthma phenotype) potential of these β2AR blockers in the HDM model of asthma.Male Balb/c mice were challenged with 25 μg HDM protein by intranasal delivery in two protocols designed to test the ‘prophylactic’ and ‘therapeutic’ effects of nadolol and carvedilol. In both protocols, chronic nadolol treatment significantly lowered the development of airway inflammation and mucus production in response to HDM, while chronic carvedilol treatment was ineffective. In addition, nadolol significantly attenuated the increased AHR response in the ‘prophylactic’ model but only moderately reduced the airway resistance in the ‘therapeutic’ model. Thus, the present studies support our previous findings in the ovalbumin model of asthma and provide further evidence to support nadolol's potential in asthma therapy.Support or Funding InformationSupported by R01AI110007