Alveolar liquid clearance in lung injury: Evaluation of the impairment of the β2-adrenergic agonist response in an ischemia-reperfusion lung injury model

Abstract

While alveolar liquid clearance (ALC) mediated by the β2-adrenergic receptor (β2-AR) plays an important role in lung edema resolution in certain models of lung injury, in more severe lung injury models, this response might disappear. Indeed, we have shown that in an ischemia-reperfusion-induced lung injury model, β2-agonists do not enhance ALC. The objective of this study was to determine if downregulation of the β2-AR could explain the lack of response to β2-agonists in this lung injury model. In an in vivo canine model of lung transplantation, we observed no change in β2-AR concentration or affinity in the injured transplanted lungs compared to the native lungs. Furthermore, we could not enhance ALC in transplanted lungs with dcAMP + aminophylline, a treatment that bypasses the β2-adrenergic receptor and is known to stimulate ALC in normal lungs. However, transplantation decreased αENaC expression in the lungs by 50%. We conclude that the lack of response to β2-agonists in ischemia-reperfusion-induced lung injury is not associated with significant downregulation of the β2-adrenergic receptors but is attributable to decreased expression of the ENaC channel, which is essential for sodium transport and alveolar liquid clearance in the lung.