Selected Contribution: Long-term effects of β 2 -adrenergic receptor stimulation on alveolar fluid clearance in mice

• Published in: Journal of applied physiology (1985) Vol. 93; no. 5; pp. 1875 - 1880
• Main Authors: Sartori, C., Fang, X., McGraw, D. W., Koch, P., Snider, M. E., Folkesson, H. G., Matthay, M. A.
• Format: Journal Article
• Language: English
• Published: 01.11.2002
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00275.2002

Stimulation of active fluid transport with β-adrenergic receptor (βAR) agonists can accelerate the resolution of alveolar edema. However, chronic βAR-agonist administration may cause βAR desensitization and downregulation that may impair physiological responsiveness to βAR-agonist stimulation. Therefore, we measured baseline and terbutaline- (10 −3 M) stimulated alveolar fluid clearance in mice that received subcutaneously (miniosmotic pumps) either saline or albuterol (2 mg · kg −1 · day −1 ) for 1, 3, or 6 days. Continuous albuterol administration increased plasma albuterol levels (10 −5 M), an effect that was associated with 1) a significant decrease in βAR density and 2) attenuation, but not ablation, of maximal terbutaline-induced cAMP production. Forskolin-mediated cAMP-release was unaffected. Continuous albuterol infusion stimulated alveolar fluid clearance on day 1 but did not increase alveolar fluid clearance on days 3 and 6. However, terbutaline-stimulated alveolar fluid clearance in albuterol-treated mice was not reduced compared with saline-treated mice. Despite significant reductions in βAR density and agonist-mediated cAMP production by long-term βAR-agonist exposure, maximal βAR-agonist-mediated increase in alveolar fluid clearance is not diminished in mice.