期刊
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
卷 32, 期 1, 页码 52-58出版社
AMER THORACIC SOC
DOI: 10.1165/rcmb.2004-0177OC
关键词
mechanical ventilation; nucleotide; purinoceptor; ventilator-induced lung injury
资金
- NHLBI NIH HHS [1 K08 HL72836-01] Funding Source: Medline
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [K08HL072836] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM008450] Funding Source: NIH RePORTER
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; (H) tidal volume (VT; 6 ml/kg); (iii) VT (6 ml/kg) and positive end-expiratory pressure (PEEP; 5 cm H2O); (iv) VT (12 ml/kg); or (v) VT (12 ml/kg) and PEEP (5 cm H2O)Bronchoalveolar lavage (BAL) was analyzed for adenyl-nucleotides. Pulmonary, hepatic, and renal tissues were assessed for P2Y4, P2Y6, P2X7, A(3), and A(2b) 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 A(2b) mRNA and decreased P2X7 in the lung; mRNA changes in lung Fas ligand paralleled P2X7. PEEP normalized BAL nucleotide profiles and A(2b) expression. Injurious MV reduced hepatic and renal P2X7 mRNA; PEEP normalized these levels in both tissues. Large-volume MV also decreased renal A(2b) 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.
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