title: Inducible cyclooxygenase expression mediating hypoxia/reoxygenation-induced pulmonary vasoconstriction is attenuated by a cyclooxygenase inhibitor in rats.
abstract: OBJECTIVE
  Hypoxic pulmonary vasoconstriction (HPV) is a well known phenomenon to temporarily offset a ventilation-perfusion mismatch. Sustained HPV may lead to pulmonary hypertension. In this protocol, we studied the relationships between the HPV response and inducible cyclooxygenase II (COX II) activation after hypoxia-reoxygenation (H-R) challenge in an isolated perfused lung model.
  
  
  METHODS
  An in situ isolated perfused rat lung model underwent inaction of hypoxia by ventilation with 5% CO(2)-95% N(2) for 10 minutes instead of 5% CO(2)-95% air; they were then reoxygenated with 5% CO(2)-95% air. We measured pulmonary arterial pressure (PAP) changes before, during, and after H-R challenge. We also estimated changes in blood concentrations of hydroxyl radicals, nitric oxide (NO) and thromboxane B(2) (TxB(2)) before and after H-R as well as mRNA expressions of COX II in lung tissue thereafter. A COX II inhibitor, celecoxib (10 mg/kg), was administered between 2 consecutive challenges.
  
  
  RESULTS
  Hypoxia induced pulmonary vasoconstriction by increasing PAP (4.1 ± 0.8 mm Hg). Consecutive hypoxic challenges did not show tachyphylaxis (P > .05). H-R of lung tissues induced significant increases in blood concentrations of hydroxyl radicals (48.5 ± 7.6 vs 75.8 ± 11.5 mmol/L; P < .01), NO (54.3 ± 12.3 vs 77.7 ± 15.7 pmol; P < .05), and TxB(2) (42.3 ± 6.9 vs 58.7 ± 8.6 pg/mL; P < .05). Lung tissue H-R also significantly increased COX II mRNA expression compared with sham tissues (1 ± 0 vs 4.0 ± 2.8; P < .001). The COX II inhibitor celecoxib significantly attenuated HPV responses (P < .05) and attenuated the elevated blood concentrations of TxB(2) (P < .05), hydroxyl radicals (P < .01), nitric oxide (P < .05), and COX II mRNA expression (P < .05) after H-R challenge.
  
  
  CONCLUSIONS
  Lung tissue H-R induced significant increases blood concentrations of inflammatory mediators and tissue mRNA expression of COX related to elevation of HPV responses. COX II inhibitor celecoxib attenuated the HPV responses by reducing TxB(2) release.
authors.affiliation: Department of Chemistry, Graduate Institute of Basic Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
authors.forename: C L
authors.initials: CL
authors.lastname: Su
authors.forename: D W
authors.initials: DW
authors.lastname: Yuan
authors.forename: L L
authors.initials: LL
authors.lastname: Chiang
authors.forename: H L
authors.initials: HL
authors.lastname: Lee
authors.forename: K H
authors.initials: KH
authors.lastname: Chen
authors.forename: D
authors.initials: D
authors.lastname: Wang
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D017665:Hydroxyl Radical / Q000097:blood; D000860:Hypoxia / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000097:blood; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D010477:Perfusion; D011651:Pulmonary Artery / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D011720:Pyrazoles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000097:blood; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D052246:Cyclooxygenase 2 Inhibitors; D018836:Inflammation Mediators; D011720:Pyrazoles; D012333:RNA, Messenger; D013449:Sulfonamides; D009569:Nitric Oxide; D017665:Hydroxyl Radical; D013929:Thromboxane B2; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D000068579:Celecoxib