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

Abstract

While alveolar liquid clearance (ALC) mediated by the β-adrenergic receptor (β-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, β-agonists do not enhance ALC. The objective of this study was to determine if downregulation of the β-AR could explain the lack of response to β-agonists in this lung injury model. In an in vivo canine model of lung transplantation, we observed no change in β-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 β-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 β-agonists in ischemia-reperfusion-induced lung injury is not associated with significant downregulation of the β-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.