Takashi Suzuki

Effects of Histamine H2-Receptor Antagonists and a Proton Pump Inhibitor on the Mucosal Hydroxyproline Content of Ethanol-HCI-lnduced Gastric Lesions in Rats

We evaluated the effects of different antisecretory agents (H2-receptor antagonists and a proton pump inhibitor) on collagen regeneration in rat gastric lesions induced by intragastric administration of 50% ethanol +0.15 N HCl (EtOH-HCl). The lesion indices showed the highest value 30 min after administration of EtOH-HCl and a significantly decreased value 15 h later. The mucosal hydroxyproline concentration was significantly increased 30 min after EtOH-HCl administration, reached a maximum 6 h later and subsequently decreased as time passed. Intraperitoneal administration of cimetidine at a dose of 100 mg/kg or famotidine at a dose of 5 mg/kg 30 min after EtOH-HCl administration could not reduce the lesion indices in less than 24 h and suppressed the increase in mucosal hydroxyproline concentrations significantly compared with the control group. On the other hand, treatment with 10 mg/kg of E-3810, a proton pump inhibitor, had no effects on the lesion healing nor on the fluctuation of mucosal hydroxyproline concentrations. These facts suggest that H2-receptor antagonists might delay the healing of EtOH-HCl-induced gastric lesions through the suppression of collagen regeneration under the condition of exclusion of gastric acid secretion.

Effect of Duodenal Mucosal Blood Flow on Duodenal Alkaline Secretion in Rats

To investigate the role of duodenal mucosal blood flow (DMBF) in the regulation of duodenal alkaline secretion (DAS), both parameters were measured before and after the administration of various drugs in rats. The DMBF was determined using an electrolytically generated hydrogen gas clearance technique, and the DAS was measured by the perfusion method. The administration of dulcerozine, a potent duodenal ulcerogenic agent, at a dose of 250 mg/kg and serotonin at a dose of 20 mg/kg, which produces duodenal ulcerations with an acid load, decreased both DMBF and DAS. On the other hand, the administration of secretin at a dose of 10 U/kg increased both parameters. There were parallel changes in DMBF and DAS. It is concluded, therefore, that DAS may be regulated by DMBF and that both parameters may be involved in the defense mechanism of duodenal mucosa.

Serotonin-Induced Decrease of Duodenal Mucosal Blood Flow plus Acid Load Produces Duodenal Mucosal Lesion in Rats

To clarify the role of duodenal mucosal blood flow in the genesis of duodenal mucosal lesions, a single dose of serotonin, 20 mg/kg, was administered subcutaneously to rats. Serotonin significantly decreased both the duodenal mucosal blood flow and the output of gastric acid and pepsin. However, mild duodenal erosions were observed in only 2 of the 9 rats receiving that agent. The repeated intragastric administration of 1 ml of 0.1 N HCl hourly for 6 h failed to induce duodenal mucosal lesions. On the other hand, the administration of both serotonin and repeated doses of HCl produced marked duodenal mucosal lesions in all rats. It is concluded, therefore, that one of the factors responsible for the genesis of duodenal mucosal lesions is a decrease of duodenal mucosal blood flow combined with an acid load against the duodenal mucosa.