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Repeated Bouts of Moderate-Intensity Aerobic Exercise Reduce Airway Reactivity in a Murine Asthma Model

¹ Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, Alabama; and ² Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio

Correspondence and requests for reprints should be addressed to Lisa M. Schwiebert, Ph.D., Department of Physiology and Biophysics, MCLM, Room 955, University of Alabama at Birmingham, 1918 University Boulevard, Birmingham, AL 35294-0005. E-mail: lschwieb{at}uab.edu

We have reported that moderate-intensity aerobic exercise training attenuates airway inflammation in mice sensitized/challenged with ovalbumin (OVA). The current study determined the effects of repeated bouts of aerobic exercise at a moderate intensity on airway hyperresponsiveness (AHR) in these mice. Mice were sensitized/challenged with OVA or saline and exercised at a moderate intensity 3 times/week for 4 weeks. At protocol completion, mice were analyzed for changes in AHR via mechanical ventilation. Results show that exercise decreased total lung resistance 60% in OVA-treated mice as compared with controls; exercise also decreased airway smooth muscle (ASM) thickness. In contrast, exercise increased circulating epinephrine levels 3-fold in saline- and OVA-treated mice. Because epinephrine binds β₂-adrenergic receptors (AR), which facilitate bronchodilatation, the role of β₂-AR in exercise-mediated improvements in AHR was examined. Application of the β₂-AR antagonist butoxamine HCl blocked the effects of exercise on lung resistance in OVA-treated mice. In parallel, ASM cells were examined for changes in the protein expression of β₂-AR and G-protein receptor kinase-2 (GRK-2); GRK-2 promotes β₂-AR desensitization. Exercise had no effect on β₂-AR expression in ASM cells of OVA-treated mice; however, exercise decreased GRK-2 expression by 50% as compared with controls. Exercise also decreased prostaglandin E₂ (PGE₂) production 5-fold, but had no effect on E prostanoid-1 (EP1) receptor expression within the lungs of OVA-treated mice; both PGE₂ and the EP1 receptor have been implicated in β₂-AR desensitization. Together, these data indicate that moderate-intensity aerobic exercise training attenuates AHR via a mechanism that involves β₂-AR.

Key Words: asthma • airway hyperresponsiveness • exercise • β₂-adrenergic receptor

CLINICAL RELEVANCE This is the first report to demonstrate that aerobic exercise at a moderate intensity attenuates airway hyperresponsiveness via a mechanism that involves the β2-adrenergic receptor. Because increased airway hyperresponsiveness is a hallmark of the asthmatic response, this study supports the use of moderate-intensity aerobic exercise as an adjunct therapy for the treatment of this chronic disease.