Figure 1.

Altered phosphodiesterase (PDE) activities and cyclic nucleotide levels in LPS-induced animal model of ALI. Lungs were isolated from mice treated with LPS and/or MnTMPyP as described in the Experimental procedures section. The tissue extracts were used to evaluate the protein levels of PDE2, PDE3, and PDE5 (A–C) and respective activities (D–F). LPS increases PDE3 activity and a decrease in PDE5 activity, despite no changes in protein levels. PDE activity changes were sensitive to MnTMPyP pretreatment indicative of a peroxynitrite-dependent mechanism. LPS decreased cAMP levels (G), whereas cGMP levels were increased (H). MnTMPyP pretreatment prevented these changes (G and H). Data represent mean ± SEM, n = 3 to 5. ∗p < 0.05 versus control lungs; ^†p < 0.05 versus LPS alone. ALI, acute lung injury; LPS, lipopolysaccharide; MnTMPyP, manganese (III) tetrakis(1-methyl-4-pyridyl)porphyrin.