Role of accumulated gastric content in the pathogenesis of cysteamine‐ and mepirizole‐induced duodenal ulcers in the rat

. Subcutaneous administration of cysteamine and mepirizole (at ulcerogenic and non‐ or weakly ulcerogenic doses) to fasted rats induced villous damage to the duodenum within 4 h. Only the damage induced by ulcerogenic doses progressed to macroscopically visible ulcers 10–12 h later. A considerable increase in gastric content was observed for more than 6–8 h after administration of the ulcerogenic dose of agents, but normal contents were noted 12 h later. The intraduodenal pH remained low for up to 16–20 h when ulcerogenic doses were given, but returned to control levels within 8–12 h when non‐ulcerogenic doses were given. Histamine similarly caused villous damage to the duodenum, yet there was no progression to an ulcer. Accumulation of gastric contents and a lower intraduodenal pH with histamine persisted for only 2 h and 1 h, respectively. We conclude that prolonged accumulation of gastric contents for up to 8 h together with a decreased lower intraduodenal pH for 16–20 h are necessary for the developmental progression of villous damage to well‐defined ulcers in the presence of ulcerogens.