Reserpine, vagal adrenergic activity and stress‐induced acute gastric mucosal injury in the rat.

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Abstract
1. Stress activates the hypothalamus causing central adrenergic discharge and stimulation of the autonomic sympathetic system. Reserpine produces the same effect and, therefore, its acute gastric mucosal injury is stress-induced. This injury was employed in the gastric diversion rat, a model for determining gastric acid secretion under basal conditions, to examine the relationship of the vagus nerve to the autonomic sympathetic system in the mechanism of stress-induced acute gastric mucosal injury. 2. After 6 h of reserpine (5 mg/kg I.P.), all rats developed oval or round lesions confined to the glandular stomach and of no constant relationship to rugal crests (lesion score 29 .+-. 2.7 mm2, mean .+-. S.E., n = 10). Microscopically, these lesions were vascular in origin, developing as intramural foci of haemorrhage or necrosis and expanding to communicate with the lumen. Pre-treatment with potent antisecretory doses of the anticholinergic atropine (5 mg/kg I.P.) or the H2-receptor antagonist cimetidine (40 mg/kg I.P.) did not influence this reserpine action (28 .+-. 3 mm2 and 27.5 .+-. 2.3 mm2, respectively, mean .+-. S.E., n = 10). Protection against the reserpine lesions by the .alpha.-adrenoceptor blocking drugs phenoxybenzamine or phentolamine given in a dose of 10 mg/kg I.P. was significantly (P < 0.01) more than that afforded by the 5 mg/kg I.P. dose. However, the 15 mg/kg I.P. dose was completely protective against the lesions. Vagotomy had a similar protective effect. Interruption of autonomic sympathetic delivery to the stomach by coeliac ganglionectomy had no influence on the macroscopic or microscopic effects of reserpine on the stomach (30.5 .+-. 3.4 mm2, mean .+-. S.E, n = 10). 3. The H+ output associated with 6 h of gastric diversion (61 .+-. 4.5 .mu.mol, mean .+-. S.E.) was significantly (P < 0.001) depressed by reserpine alone (26 .+-. 2 .mu.mol) or with atropine (19 .+-. 1.8 .mu.mol) or cimetidine (21 .+-. 2 .mu.mol). Protection against the reserpine lesions by phenoxybenzamine or phentolamine was associated with dose-dependent increase of H+ output, which with the 15 mg/kg dose was similar to that of control values (58 .+-. 4.1 .mu.mol and 60.3 .+-. 2.8 .mu.mol vs. 61 .+-. 4.5 .mu.mol). Vagotomy protection was associated with an H+ output significantly (P < 0.001) lower than that with reserpine alone (14 .+-. 1.4 .mu.mol). Coeliac ganglionectomy had no influence on the H+ output associated with reserpine treatment. 4. The results of this study suggest that in the rat stress produces vagal delivery of .alpha.-adrenoreceptor stimulation to the stomach, causing vasoconstriction which depresses H+ secretion and induces mucosal injury. The autonomic sympathetic system does not participate in this stress-induced action. Since the gastric diversion rat was used in this study, the results also show that duodenal contents are not required for the development of stress-induced gastric mucosal injury and suggest that H+ is not a critical factor in its mechanism.