The role of aspirin in gastric ulceration . Some factors involved in the development of gastric mucosal damage induced by aspirin in rats exposed to various stress conditions.

The gastric irritant effects of aspirin were studied in rats treated with a variety of physical and "disease" (inflammatory) stress conditions (which may mimic responses to some stress states encountered clinically) with the object of establishing whether these stress states increase the susceptibility of the gastric mucosa to the potentially ulcerogenic actions of aspirin. While exposure to physical (eg, cold) stress conditions markedly increased the sensitivity of the gastric mucosa to aspirin, exposure to various disease stressors (eg, adjuvant arthritis, acute pain, or paw inflammation) did not appreciably affect the mucosal sensitivity to this drug. Attempts were made to determine the mechanisms of the physical stress plus aspirin interaction by use of pharmacological agents. The results suggest a major involvement of the parasympathetic-vagal, sympathetic, and histamine-producing systems, but not the adrenocortical axis, in this model of gastric ulcerogenesis. No differences were observed in the mucosal uptake of [14C]aspirin, showing that accelerated uptake of the drug is not a factor in the development of gastric ulceration.