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

• Published in: Nihon yakurigaku zasshi Vol. 112; no. 2; p. 117
• Main Authors: Arai, H, Mizuo, M, Marubuchi, S, Nakagawa, M, Mori, Y
• Format: Journal Article
• Language: Japanese
• Published: Japan 01.08.1998
• Subjects: Animals; Anti-Inflammatory Agents - adverse effects; Anti-Ulcer Agents - pharmacology; Gastric Mucosa - blood supply; Guanidines - pharmacology; Histamine H2 Antagonists - pharmacology; Immersion - adverse effects; Indomethacin - adverse effects; Male; Nitric Oxide - physiology; Peptic Ulcer Hemorrhage - drug therapy; Peptic Ulcer Hemorrhage - etiology; Rats; Rats, Wistar; Regional Blood Flow - drug effects; Steroids; Stimulation, Chemical; Stomach Ulcer - drug therapy; Stomach Ulcer - etiology; Stress, Physiological - complications; Sulfones - pharmacology
• ISSN: 0015-5691
• DOI: 10.1254/fpj.112.117

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.