Pathophysiological roles of arachidonic acid metabolites in rat dental pulp.

Arachidonic acid metabolism in normal rat incisor pulp was examined by measuring the conversion activity of exogenously added arachidonic acid in pulpal homogenates. It was demonstrated that the major metabolites were 12-hydroxyeicosatetraenoic acid and prostaglandin (PG) I2. Immunohistochemical studies revealed that PGI2 synthase was distributed in the pulpal blood-vessel cells, fibroblasts and odontoblasts, suggesting that PGI2 may contribute to regulating the function of these cells. When the incisor pulp was experimentally inflamed by applying lipopolysaccharide, arachidonic acid metabolism in the pulp showed overall increase. Change in the pulpal vascular permeability, which was assessed by quantifying the amount of extravasated dye, was almost parallel to the changes in PGE2 and PGI2 production. When production of the PGs was inhibited by indomethacin, the increase of vascular permeability in the inflamed pulp was also suppressed. Topically-applied PGE2 and PGI2 methyl ester abolished the suppression of increase in vascular permeability by indomethacin. These results suggest that PGE2 and PGI2 may be involved in the increase of vascular permeability in the experimental pulp inflammation. We further measured the production of leukotriene (LT) B4 in the inflamed pulp by incubating isolated pulp samples with Ca ionophore A23187, followed by radioimmunoassay. Change in LTB4 production was revealed to be almost parallel to that of neutrophil infiltration. BW755C, an inhibitor of both cyclooxygenase and lipoxygenase, reduced both LTB4 production and neutrophil infiltration. Accordingly, it was suggested that LTB4 may be involved in neutrophil infiltration in the experimental pulp inflammation.