title: Reserpine, vagal adrenergic activity and stress-induced acute gastric mucosal injury in the rat.
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 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)
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000293:injuries* / Q000473:pathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology*; D013312:Stress, Physiological / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000502:physiology*; D014630:Vagus Nerve / Q000502:physiology*
chemical_list: D000317:Adrenergic alpha-Antagonists; D001285:Atropine; D002927:Cimetidine; D012110:Reserpine