Lung edema clearance: 20 years of progress selected contribution: Long-term effects of beta(2)-adrenergic receptor stimulation on alveolar fluid clearance in mice

Lung edema clearance: 20 years of progress selected contribution: Long-term effects of beta(2)-adrenergic receptor stimulation on alveolar fluid clearance in mice

Sartori C; Fang X; McGraw D W; Koch P; Snider M E; Folkesson H G; Matthay M A

Journal of Applied Physiology

2002

2002-11

Stimulation of active fluid transport with beta-adrenergic receptor (betaAR) agonists can accelerate the resolution of alveolar edema. However, chronic betaAR-agonist administration may cause betaAR desensitization and downregulation that may impair physiological responsiveness to betaAR-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 betaAR 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 betaAR density and agonist-mediated cAMP production by long-term betaAR-agonist exposure, maximal betaAR-agonist-mediated increase in alveolar fluid clearance is not diminished in mice.

acute lung injury; alveolar; beta-adrenergic-receptor; desensitization; down-regulation; epithelium; hydrostatic pulmonary-edema; in-vivo; liquid clearance; lung fluid balance; messenger-rna; Physiology; pulmonary edema; rat lung; resolution; sodium transport; Sport Sciences

Journal Article

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1875-1880

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