Published ahead of print on September 23, 2004, doi:10.1165/rcmb.2004-0177OC Am. J. Respir. Cell Mol. Biol., Volume 32, Number 1, January 2005, 52-58 A more recent version of this article appeared on January 1, 2005
Submitted on June 2, 2004 Mechanical Ventilation Alters Airway Nucleotides and Purinoceptors in Lung and Extrapulmonary OrgansChristelle D Douillet1,1 Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 2 Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA * To whom correspondence should be addressed. E-mail: prich{at}med.unc.edu.
Extracellular nucleotides are stress-responsive ligands that mediate a variety of cellular processes via purinoceptors. We hypothesized that mechanical ventilation (MV) would alter the extracellular adenyl-nucleotide profile and purinoceptor expression in lung and extrapulmonary tissues. Twenty-eight rats were randomized to: 1) unventilated controls, 2) Vt 6ml/kg, 3) Vt 6 ml/kg, PEEP (5 cm H20), 4) Vt 12 ml/kg, or 5) Vt 12 ml/kg, PEEP. Bronchoalveolar lavage (BAL) was analyzed for adenyl-nucleotides. Pulmonary, hepatic, and renal tissues were assessed for P2Y4, P2Y6, P2X7, A3, and A2b receptor expression by real-time RT-PCR and Fas/FasL mRNA was quantified in the lung. MV produced volume-dependant changes in BAL nucleotides; AMP and adenosine increased whereas ATP and ADP proportions decreased. Large-volume MV increased A2b mRNA and decreased P2X7 in the lung; mRNA changes in lung FasL paralleled P2X7. PEEP normalized BAL nucleotide profiles and A2b expression. Injurious MV reduced hepatic and renal P2X7 mRNA; PEEP normalized these levels in both tissues. Large-volume MV also decreased renal A2b mRNA. Mechanical ventilation alters the BAL adenyl-nucleotide profile and purinoceptor patterns in lung, liver, and kidney. PEEP normalizes the BAL nucleotide profile and receptor patterns in lung and extrapulmonary tissues.
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