Inhibitory Effects of Histamine Receptor Antagonist on Stress Ulcer

Cold restraint ulcers were produced in rats for use as models for stress ulcers, and the inhibitory effects of histamine H1- and H2-receptor antagonists on ulcerogenesis were studied from the view points of gastric acidity, intra-gastric mucosal content of histamine and microvasculature of the gastric mucosa. The following results were obtained.

1. Both diphenhydramine, an H1-antagonist, and cimetidine, an H2-antagonist, successfully inhibited development of cold restraint ulcers.

2. Study of gastric acidity at time of cold restraint ulcer formation failed to demonstrate a state of hyperchlorhydria in the control group, diphenhydramine group and cimetidine group.

3. The microvasculature under cold restraint showed disturbance of microcirculation in the gastric mucosa due to stasis of blood in the control group, but blood flow was good in both the diphenhydramine and cimetidine administered groups.

4. The histamine content in the gastric mucosa under cold restraint showed a rapid change in pattern in the control group from a significant decrease 30 minutes after cold restraint to a significant increase at 120 minutes. The diphenhydramine administered group presented a histamine release inhibitory pattern while the cimetidine administered group showed a change in pattern similar to the controls.

From the above results, it is noted that the histamine released from the gastric mucosa under cold restraint acts upon the microvasculature rather than gastric acid secretion, and induces disturbance of the microcirculation causing devitalization of the gastric mucosa due to hypoxia, and thus contributes to ulcerogenesis. At this time, it is considered that diphenhydramine with its powerful sedative effect on the brain reduces the brain reaction to stress and secondarily inhibits release of histamine, while cimetidine blocks, at the histamine H2-receptor site, the vascular effects of histamine released under cold restraint and prevents the development of microcirculatory disturbance. Therefore, when the development of acute gastro-duodenal mucosal lesions (AGML) can be anticipated clinically, it is felt the administration of histamine receptor antagonist can provide some degree of preventive action towards AGML.