Inducible cyclooxygenase expression mediating hypoxia/reoxygenation-induced pulmonary vasoconstriction is attenuated by a cyclooxygenase inhibitor in rats

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 2 (42.3 ± 6.9 vs 58.7 ± 8.6 pg/mL; P 2 (P 2 release.