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This Article Full Text Full Text (PDF) All Versions of this Article: 297/4/L785    most recent 00096.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Yu, E. N. Z. Articles by Davis, I. C. PubMed PubMed Citation Articles by Yu, E. N. Z. Articles by Davis, I. C.

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

Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio

Submitted 23 March 2009 ; accepted in final form 7 August 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 β-agonists stimulated AFC at 10 cmH₂O P by upregulating amiloride-sensitive Na⁺ transport. However, at 18 cmH₂O P, PKA agonists and β-agonists reduced AFC. At 15 cmH₂O P, the AFC rate was intermediate (mean 26.6%), and forskolin and β-agonists had no effect. Comparable P dependency of AFC and β-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 A_2b-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 β-agonists. These findings indicate that, in the normal mouse lung, basal AFC rates and responses to β-agonists are impacted by ventilation pressure in an adenosine-dependent manner.

tidal volume; epithelial sodium channel; adenosine