Repeated bouts of moderate-intensity aerobic exercise reduce airway reactivity in a murine asthma model.
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 beta(2)-adrenergic receptors (AR), which facilitate bronchodilatation, the role of beta(2)-AR in exercise-mediated improvements in AHR was examined. Application of the beta(2)-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 beta(2)-AR and G-protein receptor kinase-2 (GRK-2); GRK-2 promotes beta(2)-AR desensitization. Exercise had no effect on beta(2)-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 E(2) (PGE(2)) production 5-fold, but had no effect on E prostanoid-1 (EP1) receptor expression within the lungs of OVA-treated mice; both PGE(2) and the EP1 receptor have been implicated in beta(2)-AR desensitization. Together, these data indicate that moderate-intensity aerobic exercise training attenuates AHR via a mechanism that involves beta(2)-AR.
Hewitt
Matt
M
Department of Physiology and Biophysics, University of Alabama at Birmingham, 1918 University Boulevard, Birmingham, AL 35294-0005, USA.
Estell
Kim
K
Davis
Ian C
IC
Schwiebert
Lisa M
LM
D000332:Aerobiosis; D000403:Airway Resistance / Q000502:physiology; D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D001249:Asthma / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004837:Epinephrine / Q000097:blood; D005260:Female; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009130:Muscle, Smooth / Q000473:pathology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010805:Physical Conditioning, Animal / Q000379:methods*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000378:metabolism; D058306:Receptors, Prostaglandin E, EP1 Subtype; D012130:Respiratory Hypersensitivity / Q000503:physiopathology / Q000628:therapy
D000485:Allergens; C545636:Ptger1 protein, mouse; D018343:Receptors, Adrenergic, beta-2; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D010047:Ovalbumin; C496568:GRK2 protein, mouse; D054769:G-Protein-Coupled Receptor Kinase 2; D015232:Dinoprostone; D004837:Epinephrine