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

Abstract

SUMMARY1. 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 a-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 ,tmol, mean +S.E.) was significantly (P < 0-001) depressed by reserpine alone (26 + 2 jtmol) or with atropine (19+1-8,imol) or cimetidine (21+2,tmol). Protection against the reserpine lesions by phenoxybenzamine or phentolamine was associated with dosedependent increase of H+ output, which with the 15 mg/kg dose was similar to that of control values (58 + 4-1 ,tmol and 60-3 + 2-8 ,mol vs. 61 + 4-5 /tmol). Vagotomy protection was associated with an H+ output significantly (P < 0-001) lower than that with reserpine alone (14 + 1-4 jumol). 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 a-adrenoceptor 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.

Role of Oxygen-Derived Free Radicals in the Mechanism of Chronic Gastric Ulceration in the Rat: Implications for Cytoprotection

“…This ulceration has been shown to result from persistence of the reserpine-induced acute ischaemic injury of the gastric mucosa [7,9], Reserpine-induced chronic gastric ulcer ation was reproduced in this study and was associated with normochlorhydria (table 2). Dose-dependent protection of the rat stom ach against this ulceration was afforded by allopurinol and DMSO, a complete protec tion was noted with 5% solutions (table 2).…”

“…Parenteral administration of large doses of reserpine produces vagal a-adrenoceptor stimulation to intragastric blood vessels causing mucosal ischaemia, and persistence of this stimulation produces chronic gastric ulceration [7,9]. There is no pharmacologi cal evidence that allopurinol or DMSO inter feres with any of these actions.…”

“…This injury is ischaemic and results from vagal a-adrenoceptor stimulation to gastric submucosal and mucosal blood vessels caus ing vasoconstriction [9]. Intraperitoneal in jection of 5 mg/kg of reserpine for 5 days produces chronic gastric ulceration of the rat stomach within 4 weeks [7], This observa tion indicates that gastric mucosal ischaemia is the principal factor in the mechanism of development of chronic gastric ulceration.…”

Effect of psychogenic stress on gastrointestinal function

“…There is overwhelming evidence that vagotomy or cholinergic blockade is beneficial in gastric ulceration induced by stress or pharmacologically (TRH, CRH) (11,13,25,30,81,157,160,172,185,197). In fact, administration of acetylcholine or physostigmine alone is sufficient to cause damage or aggravate stress injury (13,49,155,209).…”

Effects on neuroendocrinoimmune network of Lizhong Pill in the reserpine induced rats with spleen deficiency in traditional Chinese medicine

“…It is composed of Radix Ginseng (Panax ginseng C.A. Meyer), Rhizoma Zingiberis (Zingiber officinale Roscoe), and Vogt, 1960), adrenaline (A), dopamine (DA) (Ellison and Bresler, 1974;Huang et al, 2004), which in turn induce some peripheral sympathetic symptoms, such as behavioral depression, low body temperature, bad appetite, inactiveness and diarrhea, gastric mucosal injury (Salim, 1987). These symptoms are conformed to spleen deficiency pattern in TCM (Ellison and Bresler, 1974;Huang et al, 2004), and the reserpine treated rats have been taken as an animal model for TCM spleen deficiency pattern (Gao et al, 2009).…”