Upregulation of Alveolar Epithelial Active Na + Transport Is Dependent on β 2 -Adrenergic Receptor Signaling
- 30 April 2004
- journal article
- research article
- Published by Wolters Kluwer Health in Circulation Research
- Vol. 94 (8) , 1091-1100
- https://doi.org/10.1161/01.res.0000125623.56442.20
Abstract
Alveolar epithelial beta-adrenergic receptor (betaAR) activation accelerates active Na+ transport in lung epithelial cells in vitro and speeds alveolar edema resolution in human lung tissue and normal and injured animal lungs. Whether these receptors are essential for alveolar fluid clearance (AFC) or if other mechanisms are sufficient to regulate active transport is unknown. In this study, we report that mice with no beta1- or beta2-adrenergic receptors (beta1AR-/-/beta2AR-/-) have reduced distal lung Na,K-ATPase function and diminished basal and amiloride-sensitive AFC. Total lung water content in these animals was not different from wild-type controls, suggesting that betaAR signaling may not be required for alveolar fluid homeostasis in uninjured lungs. Comparison of isoproterenol-sensitive AFC in mice with beta1- but not beta2-adrenergic receptors to beta1AR-/-/beta2AR-/- mice indicates that the beta2AR mediates the bulk of beta-adrenergic-sensitive alveolar active Na+ transport. To test the necessity of betaAR signaling in acute lung injury, beta1AR-/-/beta2AR-/-, beta1AR+/+/beta2AR-/-, and beta1AR+/+/beta2AR+/+ mice were exposed to 100% oxygen for up to 204 hours. beta1AR-/-/beta2AR-/- and beta1AR+/+/beta2AR-/- mice had more lung water and worse survival from this form of acute lung injury than wild-type controls. Adenoviral-mediated rescue of beta2-adrenergic receptor (beta2AR) function into the alveolar epithelium of beta1AR-/-/beta2AR-/- and beta1AR+/+/beta2AR-/- mice normalized distal lung beta2AR function, alveolar epithelial active Na+ transport, and survival from hyperoxia. These findings indicate that betaAR signaling may not be necessary for basal AFC, and that beta2AR is essential for the adaptive physiological response needed to clear excess fluid from the alveolar airspace of normal and injured lungs.Keywords
This publication has 29 references indexed in Scilit:
- Update on current concepts of the molecular basis of β2-adrenergic receptor signalingJournal of Allergy and Clinical Immunology, 2002
- Characterization of a Hyperdynamic Murine Model of Resuscitated Sepsis Using EchocardiographyAmerican Journal of Respiratory and Critical Care Medicine, 2001
- Adenovirus-Mediated Transfer of an Na+/K+-ATPase β1Subunit Gene Improves Alveolar Fluid Clearance and Survival in Hyperoxic RatsHuman Gene Therapy, 2000
- Role of endogenous cortisol in basal liquid clearance from distal air spaces in adult guinea‐pigsThe Journal of Physiology, 1999
- LIGHT, a novel ligand for lymphotoxin beta receptor and TR2/HVEM induces apoptosis and suppresses in vivo tumor formation via gene transfer.Journal of Clinical Investigation, 1998
- Adrenal Epinephrine Increases Alveolar Liquid Clearance in a Canine Model of Neurogenic Pulmonary EdemaAmerican Journal of Respiratory and Critical Care Medicine, 1998
- Alveolar fluid clearance in the resected human lung.American Journal of Respiratory and Critical Care Medicine, 1994
- Stimulation of lung epithelial liquid clearance by endogenous release of catecholamines in septic shock in anesthetized rats.Journal of Clinical Investigation, 1994
- Contribution of active Na+ and Cl− fluxes to net ion transport by alveolar epitheliumRespiration Physiology, 1991
- Beta-adrenergic agonists increase lung liquid clearance in anesthetized sheep.Journal of Clinical Investigation, 1987