Abstract
We studied to see whether or not endothelin, a potent vasoconstrictive peptide, is involved in the propagation of DIC in rats induced with lipopolysaccharide (LPS) by simultaneously giving animals an endothelin receptor antagonist, TAK-044. Fifty mg/kg of LPS and TAK-044 (2, 10 and 50 mg/kg) were given to the Wistar strain rats via their tail vein over a period of 4 hours for LPS and 4 1/2 hours for TAK-044, the start of administration of the latter having been 1/2 hour prior to administraion of LPS. The prothrombin time, platelet counts and plasma levels of the thrombin-antithrombin complex (TAT) and fibrinogen remained unchanged, but that of the D-dimer increased significantly. On the other hand, the levels in plasma of creatinine and alanine aminotransferase (ALT), known as markers for the organ damages, were found to be decreased in a dose-dependent fashion of TAK-044. Fibrin deposition in the glomeruli was also found to be decreased. The data altogether suggest that endothelin plays a certain role in the development of organ injuries in the LPS-induced DIC in rats.
