Mechanical ventilation alters airway nucleotides and purinoceptors in lung and extrapulmonary organs.
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: (i) unventilated control animals; (ii) tidal volume (VT; 6 ml/kg); (iii) VT (6 ml/kg) and positive end-expiratory pressure (PEEP; 5 cm H20); (iv) VT (12 ml/kg); or (v) VT (12 ml/kg) and PEEP (5 cm H20). 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 reverse transcriptase-polymerase chain reaction and Fas/Fas ligand mRNA was quantified in the lung. MV produced volume-dependent 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 Fas ligand 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. MV 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.
Douillet
Christelle D
CD
Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7228, USA.
Robinson
William P
WP
Zarzaur
Ben L
BL
Lazarowski
Eduardo R
ER
Boucher
Richard C
RC
Rich
Preston B
PB
D000241:Adenosine / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D018893:Bronchoalveolar Lavage; D053222:Fas Ligand Protein; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D009711:Nucleotides / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011983:Receptors, Purinergic / Q000378:metabolism*; D012121:Respiration, Artificial / Q000379:methods*; D012137:Respiratory System / Q000378:metabolism*
D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D009711:Nucleotides; D011983:Receptors, Purinergic; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000241:Adenosine