Figure 3.

Mechanical ventilation induces COX-2 expression and activity. Lung expression of COX-2 was determined by Western blotting and quantitative real-time PCR analysis. (A) HTV mechanical ventilation significantly increased COX-2 protein expression, compared with control and LTV mice. No significant differences in COX-1 expression were evident between the three groups. (Results were repeated in triplicate, and representative images are shown). (B) No differences were evident in COX-2 mRNA expression between the three groups. BAL and plasma prostanoids were measured as markers for cyclooxygenase activity. HTV mechanical ventilation significantly increased lavage concentrations of both prostaglandin E2 (PGE2) (C) and 6-keto prostaglandin F1α (D), a stable prostacyclin metabolite, compared with control samples. Likewise, HTV mechanical ventilation increased plasma PGE2 (E) compared with control and LTV mice, but exerted no effect on plasma 2,3-dinor-6-keto prostaglandin F1α (2,3-dinor-6-keto PGF1α) (F), a stable prostacyclin metabolite. The pharmacologic inhibition of COX-2 with CAY10404 significantly decreased BAL PGE2 and 6-keto PGF1α as well as plasma PGE2 in HTV mice. LTV, low tidal volume ventilation; HTV, high tidal volume ventilation; BAL, bronchoalveolar lavage. *P < 0.05 versus control values. **P < 0.05 versus HTV alone.