Effect of T-593 on gastric bleeding and lesions induced by indomethacin and water-immersion stress in rats: improving effect of T-593 on reduced gastric mucosal blood flow in rats

The effect of T-593, a novel antiulcer agent, was investigated with respect to gastric bleeding and lesions induced by indomethacin (3 mg/kg, s.c.) and water (23 degrees C) immersion stress (IM-WIS) with perfusion of HCl (0.13N) into the rat stomach. It was found that the total amounts of gastric bleeding and lesions after IM-WIS with perfusion of HCl were more significantly decreased in T-593 (1 mg/kg, i.v., 0.1 mg/kg/hr, d.i.)- and secretion (15 CU/kg/hr, d.i.)-treated rats, respectively. On the other hand, famotidine (1 mg/kg, i.v.) did not affect gastric bleeding and lesions. The gastric mucosal blood flow (GMBF) reduction was induced by IM-WIS. T-593 (0.03-0.1 mg/kg/hr, d.i.) inhibited the GMBF reduction dose-dependently. The GMBF improvement by T-593 disappeared with pretreatment of L-NAME (2 mg/kg, s.c.) and was recovered by L-arginine (50 mg/kg, i.v.). This indicates that GMBF improvement by T-593 is dependent on EDRF (NO). This interesting property of T-593 is expected to contribute to the clinical promotion of ulcer healing.