Different mode of action of cimetidine and prostaglandin on the rat gastric mucosa under stress loading by restrain and water-immersion.

Gastric mucosal blood flow and oxygen tension in the corporal mucosa gradually declined after water immersion in the control animals. Neither cimetidine nor prostaglandin E2 had any influence on the decrease of the corporal mucosal blood flow or mucosal oxygen tension during seven hours of stress loading. The stress ulceration began to occur starting three hours after cold immersion in the control rats, and the deficit of energy metabolism was attributed to reduced oxidative phosphorylation from tissue hypoxia resulting from lowered blood flow and oxygen tension under stress. Cimetidine (4 mg/kg) maintained aerobic glycolysis, continued to produce high-energy phosphates and kept the energy charge unchanged in the gastric mucosa. In addition, PG E2-Me (100 micrograms/kg) showed similar, but less marked and shorter-lived effects on aerobic glycolysis and ATP production, whereas the energy charge of the adenosine pool decreased significantly from that produced by cimetidine. These results indicated that cimetidine significantly reduced energy requirements as compared with the control and PG E2 groups due to marked inhibition of gastric secretion and produced inhibition of mucosal ulceration by water immersion. On the other hand, increased energy requirements due to the rise of cytoprotective mucoprotein production and a resultant decrease of the energy charge were seen with PG E2 as compared with cimetidine.