Yu EN, Traylor ZP, Davis IC
Effect of ventilation pressure on alveolar fluid clearance and beta-agonist responses in mice. [JOURNAL ARTICLE]
Am J Physiol Lung Cell Mol Physiol 2009 Aug 14.
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 beta-agonists stimulated AFC at 10 cmH2O P, by upregulating amiloride-sensitive Na(+) transport. However, at 18 cmH2O P, PKA agonists and beta-agonists reduced AFC. At 15 cmH2O 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 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 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. Key words: Ventilation pressure, Tidal volume, ENaC, Acute lung injury, Adenosine.
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