Reserpine, Vagal Adrenergic Activity and Stress-induced Acute Gastric Mucosal Injury in the Rat

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 less than 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 mumol, mean +/- S.E.) was significantly (P less than 0.001) depressed by reserpine alone (26 +/- 2 mumol) or with atropine (19 +/- 1.8 mumol) or cimetidine (21 +/- 2 mumol). 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 mumol and 60.3 +/- 2.8 mumol vs. 61 +/- 4.5 mumol). Vagotomy protection was associated with an H+ output significantly (P less than 0.001) lower than that with reserpine alone (14 +/- 1.4 mumol). Coeliac ganglionectomy had no influence on the H+ output associated with reserpine treatment.(ABSTRACT TRUNCATED AT 400 WORDS)