Several methods have been reported to produce an experimental chronic ulcer in the rat, such as thermal ulcer by Skoryna et al. (1,2), clamping-cortisone ulcer by Umebara et al. (3), and methylcholanthrene ulcer by Lauren et al. (4). In these methods thermal and clamping-cortisone ulcers seem to be valuable tools in investigation of the healing process of gastric ulcer, because of the relatively long period of its persistence and closer histologic resemblance to human peptic ulcer. However, both methods include the un desirable procedure such as the incision of glandular portion of stomach in order to perform the thermocautery of the innersurface of stomach in the former method and the consecutive administration of cortisone acetate for 8 days after the gastric operation in the latter. On the other hand, Robert and Selye (5) have reported the method to evoke an ulcer by an injection of formalin solution into the rat stomach wall itself. We also tried the same pro cedure and found the gastric necrosis corresponding to the injected area. However, the necrotic tissue did not disappear from the stomach wall even 6 days after the operation so that the so-called gastric ulcer was not produced . Then we injected the acetic acid solution, which is well known to injure the gastric mucosa (6) or to evoke inflammation in rat paw in our laboratory (7), into the rat stomach wall and found the definite gastric ulcer having resemblances to the human peptic ulcer at gross and microscopical observation. This paper deals with the studies of the healing process of the produced ulcer and the use fulness for the assay method of the curative drugs of gastric ulcer. METHODSMale rats of the Donryu strain weighing 200 to 230 g at the time of operation were used in this experiment. Under ether anesthesia laparotomy was performed through a midline epigastric incision. After exposing the stomach, 1, 10, and 30% acetic acid, 0.05 ml per animal were injected into subserosal layer in the glandular part of anterior wall, with care taken not to disturb the blood vessels. At the injection of acetic acid solu tion a thumb was placed tightly on the inserted needle in order to avoid the leak of the solution. After the injection, the needle was pull out, but the thumb was still placed on that position for at least 30 second to prevent the leak of acetic acid by removing of the

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Recently interest in investigations of adrenergic agents (stimulants and inhibitors) on gastric secretion, motility, and ulceration in experimental animals has increased (1-7). Pradhan and Wingate (6) have demonstrated that phentolamine and tolazoline enhanced the spontaneous gastric secretion in dogs while phenoxybenzamine and dichloroisopro terenol showed inhibitory effects on spontaneous as well as induced secretion by food, bethanechol, and histamine. Bass and Patterson (3) have shown that both adrenergic and adrenergic blocking agents (including phentolamine and tolazoline) possessed anti secretory properties on rat gastric secretion. Hence, if gastric acid is a primary element in experimental ulcer, adrenergic and adrenergic blocking aegnts which have antisecretory effect should inhibit gastric ulceration. However, phentolamine, MJ 1999, and isopro terenol did not affect the incidence of histamine-induced ulcer in guinea pigs (6). More over, propranolol and phenoxybenzamine increased the incidence of ulceration in fasted rats immobilized for 8 hours (7). In this study, therefore, an attempt was made to in vestigate the effect of several adrenergic blocking agents on gastric secretion and stress induced ulcer in rats and to clarify a part of the mechanism of gastric ulceration by stress. METHODSGastric secretion studies: Male Donryu strain rats (200-230 g) were used in the follow ing experiments. The animals were deprived of food for 24 hours in individual cages prior to the experiment but were allowed free access to water. Under ether anesthesia, the abdomen was incised and the junction between the pylorus and duodenum was ligated, as described by Shay et al. (8). Four hours later, the animals were killed by a blow on the head and the stomach was removed. Gastric juice was collected in a graduated test tube and the total acidity was determined by titration with 0.1 N NaOH using phenol phthalein as an indicator. The pH was determined with a glass electrode.Stress ulcer studies: As described previously by Takagi and Okabe (9), animals (235 255 g) were placed in a stress cage and immersed into a water bath (23°C) for 7 hours to the level of xiphoid process. At the end of the stress, the animals were killed by a blow * Present address:

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