| Title | Effect of ventilation pressure on alveolar fluid clearance and beta-agonist responses in mice. | | Author(s) | Yu EN, Traylor ZP, Davis IC | | Institution | Vanderbilt University. | | Source | Am J Physiol Lung Cell Mol Physiol 2009 Aug 14. | | Abstract | 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19684202 |
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