Effect of ventilation pressure on alveolar fluid clearance and beta-agonist responses in mice

• Published in: American journal of physiology. Lung cellular and molecular physiology 2009-10, Vol.297 (4), p.L785-L793
• Main Authors: Yu, Erin N Z, Traylor, Zachary P, Davis, Ian C
• Format: Article
• Language: English
• Subjects: Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists - pharmacology; Amiloride - pharmacology; Animals; Bronchoalveolar Lavage Fluid; Colforsin - pharmacology; Epithelial Cells - metabolism; Female; Lung - cytology; Lung - drug effects; Lung - metabolism; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mucociliary Clearance; Oxygen - metabolism; Pulmonary Alveoli - cytology; Pulmonary Alveoli - drug effects; Pulmonary Alveoli - metabolism; Respiration, Artificial; Respiratory Mucosa - cytology; Respiratory Mucosa - drug effects; Respiratory Mucosa - metabolism
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00096.2009

High tidal volume ventilation is detrimental to alveolar fluid clearance (AFC), but effects of ventilation pressure (P) on AFC are unknown. In anesthetized BALB/c mice ventilated at constant tidal volume (8 ml/kg), mean AFC rate was 12.8% at 6 cmH(2)O P, but increased to 37.3% at 18 cmH(2)O P. AFC rate declined at 22 cmH(2)O P, which also induced lung damage. Increased AFC at 18 cmH(2)O P did not result from elevated plasma catecholamines, hypercapnia, or hypocapnia, but was due to augmented Na(+) and Cl(-) absorption. PKA agonists and beta-agonists stimulated AFC at 10 cmH(2)O P by upregulating amiloride-sensitive Na(+) transport. However, at 18 cmH(2)O P, PKA agonists and beta-agonists reduced AFC. At 15 cmH(2)O P, the AFC rate was intermediate (mean 26.6%), and forskolin and beta-agonists had no effect. Comparable P dependency of AFC and beta-agonist responsiveness was found in C57BL/6 mice. The effect on AFC of increasing P to 18 cmH(2)O was blocked by adenosine deaminase or an A(2b)-adenosine receptor antagonist, and could be mimicked by adenosine in mice ventilated at 10 cmH(2)O P. Modulation of adenosine signaling also resulted in altered responsiveness to beta-agonists. These findings indicate that, in the normal mouse lung, basal AFC rates and responses to beta-agonists are impacted by ventilation pressure in an adenosine-dependent manner.