Denopamine stimulates alveolar fluid clearance via cystic fibrosis transmembrane conductance regulator in rat lungs

Objective: The objective of this study was to test the hypothesis that cystic fibrosis transmembrane conductance regulator (CFTR) plays a role in beta(1)-adrenergic agonist-stimulated alveolar fluid clearance. Methods: Isotonic 5% albumin solutions containing different pharmacological agents were instilled into the alveolar spaces of the isolated rat lungs. The lungs were inflated with 100% oxygen at an airway pressure of 7 cm H2O and placed in a humidified incubator at 37 degrees C. Alveolar fluid clearance was estimated by the progressive increase in the albumin concentration over 1 h. To test the hypothesis, we determined whether CFTR Cl- channel inhibitors (glibenclamide and CFTRinh-172) inhibited the effect of denopamine, a beta(1)-adrenergic agonist, on stimulation of alveolar fluid clearance in the isolated rat lungs. Results: Denopamine increased alveolar fluid clearance in a dose-dependent manner. Atenolol, a beta(1)-adrenergic antagonist, abolished the effects of denopamine on stimulation of alveolar fluid clearance. Although glibenclamide alone or CFTRinh-172 alone did not change basal alveolar fluid clearance, these CFTR inhibitors inhibited the effect of denopamine on alveolar fluid clearance. Conclusion: CFTR plays a role in beta(1)-adrenergic agonist-stimulated alveolar fluid clearance in rat lungs.