Asthma is characterized by airway obstruction, airway hyperresponsiveness (AHR) and airway inflammation. The medications used for control and acute relief of asthma may vary in effectiveness and produce serious side effects. Also, -30% of asthma patients do not achieve optimal control with any of the (SS (/) Quo ?<0 model of asthma, we have shown that chronic (28 day) administration of 13-blockers decreased AHR and produced broad anti-inflammatory effects, including dramatic changes in airway epithelium: reduced mucous production, improved morphology and increased production of I32ARs. These data suggest that the airway epithelium may be a key target affected by chronic 13-blocker therapy. Also, in a small clinical trial treating 10 mild asthmatics with the non-selective 13-blocker, nadolol, there was a dose-dependent increase in the P020 methacholine that resulted in a change of>two doubling doses in patients treated with 40 mg of nadolol. Our long-range goal is to develop 13-blockers as an alternative therapy for asthma. To make progress towards this translation, we need to understand their mechanisms of action. In this project, we will test the """"""""-w ?'
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