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

Yu EN, Traylor ZP, Davis IC. Effect of ventilation pressure on alveolar fluid clearance and -agonist responses in mice. Am J Physiol Lung Cell Mol Physiol 297: L785–L793, 2009. First published August 14, 2009; 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 cmH2O P, but increased to 37.3% at 18 cmH2O P. AFC rate declined at 22 cmH2O P, which also induced lung damage. Increased AFC at 18 cmH2O P did not result from elevated plasma catecholamines, hypercapnia, or hypocapnia, but was due to augmented Na and Cl absorption. PKA agonists and -agonists stimulated AFC at 10 cmH2O P by upregulating amiloride-sensitive Na transport. However, at 18 cmH2O P, PKA agonists and -agonists reduced AFC. At 15 cmH2O P, the AFC rate was intermediate (mean 26.6%), and forskolin and -agonists had no effect. Comparable P dependency of AFC and -agonist responsiveness was found in C57BL/6 mice. The effect on AFC of increasing P to 18 cmH2O was blocked by adenosine deaminase or an A2b-adenosine receptor antagonist, and could be mimicked by adenosine in mice ventilated at 10 cmH2O P. Modulation of adenosine signaling also resulted in altered responsiveness to -agonists. These findings indicate that, in the normal mouse lung, basal AFC rates and responses to -agonists are impacted by ventilation pressure in an adenosine-dependent manner.