Effects of antithrombin III (AT III) and Trp49-modified AT III on plasma level of 6-keto-PGF1 alpha in rats.

We evaluated the effect of antithrombin III (AT III) on the plasma level of 6-keto-PGF1 alpha in rats to determine whether AT III may promote the release of prostacyclin (PGl2) from endothelial cells in vivo. The intravenous administration of AT III (250 U/kg) significantly increased the plasma levels of 6-keto-PGF1 alpha, with a peak seen 90 min post-administration. Neither Trp49-modified AT III, which lacks affinity for heparin but retains an inhibitory capacity for thrombin, nor heparin plus AT III, increased the plasma level of 6-keto-PGF1 alpha 90 min after administration. Indomethacin pretreatment inhibited the increase in plasma levels of 6-keto-PGF1 alpha produced by AT III. Observations suggest that AT III may promote the release of PGl2 from endothelial cells by interacting with heparin-like glycosaminoglycans in vivo, consistent with previous observations in cultured endothelial cells.