[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.
Arai
H
H
Research Laboratories, Toyama Chemical Co., Ltd., Japan.
Mizuo
M
M
Marubuchi
S
S
Nakagawa
M
M
Mori
Y
Y
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000098:blood supply; D006146:Guanidines / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D007101:Immersion / Q000009:adverse effects; D007213:Indomethacin / Q000009:adverse effects; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D010438:Peptic Ulcer Hemorrhage / Q000188:drug therapy* / Q000209:etiology*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D013256:Steroids; D013268:Stimulation, Chemical; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000209:etiology; D013312:Stress, Physiological / Q000150:complications; D013450:Sulfones / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D000897:Anti-Ulcer Agents; D006146:Guanidines; D006635:Histamine H2 Antagonists; D013256:Steroids; D013450:Sulfones; C088837:T 593; D009569:Nitric Oxide; D007213:Indomethacin