INCREASED SYMPATHETIC ACTIVITY IN THE PATHOGENESIS OF RESTRAINT ULCER IN RATS

¹ Catecholamine Laboratory, West Haven Veterans Administration Hospital, West Haven, Connecticut; Departments of Medicine (Divisions of Gastroenterology, Clinical Pharmacology and Metabolism) and Pharmacology, Yale University School of Medicine, New Haven, Connecticut

Forced immobilization produced acute gastric mucosal ulcerations in 83% of rats restrained for 10 hours. Combined immobilization and cold (4°C) produced ulcerations in 96.8% of animals after two hours. Ulcerations occurred only in the glandular portion of the stomach. Fractional turnover rate, half-life and turnover rate of tritiated norepinephrine were determined in the glandular stomach, nonglandular stomach and submaxillary glands of rats subjected to restraint for 10 hours at room temperature. The norepinephrine turnover rate, which reflects the level of sympathetic activity, was significantly increased in the glandular stomach of rats subjected to restraint; there was no significant corresponding increase in nonglandular stomach or submaxillary glands. The effect of pretreatment with -methyldopa, bretylium, phenoxybenzamine and phentolamine on gastric ulceration induced by restraint for two hours at 4°C also was studied. All four drugs significantly reduced the incidence of gastric ulcerations. Adrenalectomy and pretreatment with 6-hvdroxydopamine failed to prevent restraint- and cold-induced ulcerations. The results suggest that the increased turnover of norepinephrine may be causally related to the development of restraint ulcers.

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