A biochemical and pharmacological approach to the genesis of ulcer disease. I. A model study of ethanol-induced injury to gastric mucosa in rats.

Present concepts of acute ulceration in the gastric mucosa include the hypothesis that mucosal ischemia is an important initiating event. The evidence for this is based upon observations on tissue metabolism and determinations of gastric mucosal blood flow. Using the model of gastric mucosal injury in the rat with ethanol, we have found that mucosal injury could be detected at a time when tissue oxygenation as determined by biochemical, and pharmacological studies of ATP metabolism were not compatible with ischemia. We also found that drugs acting at different subcellular levels were able to both inhibit gastric acid secretion in 4 hour pylorus-ligated rats and gastric mucosal injury after ethanol. Certain drugs, such as histamine and pentagastrin, stimulated acid secretion but inhibited the injury to the mucosa by ethanol indicating that increased cellular activity could occur during the development of mucosal injury.