Misoprostol attenuates aspirin-induced changes in potential difference and associated damage in canine gastric mucosa

Aspirin induces ulceration, cellular exfoliation, and blood loss associated with decreases in gastric mucosal potential difference (PD). Certain prostaglandins prevent the development of experimental gastric and duodenal ulcers and modify indices related to ulceration. Misoprostol, a synthetic PGE1 derivative with gastric antisecretory and mucosal protective activities, was examined at gastric antisecretory doses in dogs with Heidenhain pouches, to determine its effect on aspirin-associated changes in PD, K+ efflux, blood loss, and cell shedding, as measured by DNA release. These parameters were examined before, during, and up to 4 hours after exposure of the pouches to aspirin. Disruption of the gastric mucosal barrier (GMB) by aspirin was associated with a fall in PD and losses of K+, DNA, and blood into the pouches. Misoprostol inhibited the fall in PD and prevented blood loss over the entire period examined. Cell loss was inhibited only during the recovery period immediately following aspirin. The effect of misoprostol on GMB is consistent with studies in which prostaglandins preserve the GMB and prevent necrotic ulcerations while allowing superficial cell damage.