Restraint-induced Stress Research Articles

Restraint-induced stress ulcer. I. Hypothalamic, urinary, and adrenal biochemical studies.

AbstractThe purpose of these experiments was to study the incidence of stress ulcers in restrained rats and to correlate it with hypothalamic and adrenal cortical and medullary activity, with and without vagotomy. A total of 217 adult rats were used, grouped into 56 sets, and distributed at random in 5 experimental groups. Restraint was followed by a 79% incidence of ulceration in the glandular portion of the gastric mucosa. Vagotomy made these worse (p<0.01). Hypothalamic levels of catecholamines and serotonin showed no significant changes. Urinary measurements revealed decreased excretion of 17‐ketosteroids (p<0.001), increased excretion of uropepsinogen (p<0.01), and no significant changes in vanillylmandelic acid among the rats submitted to immobilization. In the adrenal glands of stressed animals, there was a decreased level of catecholamines (p<0.01) and no significant changes in corticosteroid content (17‐ketosteroids). These results suggest that hypothalamic stimulation and the participation of the adrenal glands are not essential factors in the pathogenesis of restraint‐induced experimental stress ulcer.

Pentagastrin protects against stress ulceration in rats

Stress ulcer formation was examined in the following four groups of 18 rats each: (a) chow fed, (b) fed an isocaloric amount of a liquid diet, (c) fed a liquid diet plus pentagastrin injections (250 μg/kg, 3 times/ day), and (d) fed a liquid diet plus histamine (20 mg/ kg, 3 times/day). The diet regimen lasted 10 days, and injections of saline, pentagastrin, or histamine were given over the last 7 days before water immersion induced stress. Six rats from each group were killed before stress (zero time) and after 4 and 20 hr of stress. Serum gastrin and oxyntic gland mucosal DNA synthesis were significantly lower before stress in all liquid-fed rats compared with chow-fed controls. At this time, the ulcer index was zero in all groups. DNA synthesis decreased, and the ulcer index increased progressively in all groups with exposure to stress. After 4 hr of stress, the ulcer index was 3.8 in the group receiving pentagastrin, compared with 14.1 and 10.7 in the animals receiving liquid diet alone or liquid diet with histamine injections, respectively. During stress, DNA synthesis in the group receiving pentagastrin decreased significantly less than in all other groups. There was significant correlation (r = 0.782; P < 0.01) between ulcer index and the decrease in DNA synthesis. The authors conclude that rats fed liquid diets are more susceptible to restraint-induced stress ulcers because of their lower endogenous gastrin levels and that exogenous pentagastrin increases the resistance of these animals to ulceration. The susceptibility of all groups of animals to stress ulceration was directly correlated with decreases in DNA synthesis.

Effects of somatostatin on gastric mucosal histamine and serotonin content in restrained rats.

The effects of continuous intravenous perfusion of somatostatin on the incidence of ulcers and the histamine and serotonin gastric mucosal content in rats subjected to 12 h of restraint were studied. 51 sets of Sprague-Dawley male rats (102 animals) were divided at random into two groups. Those in group I were immobilized and treated with an intravenous infusion of isotonic saline solution. Animals in group II were also immobilized and given intravenous cyclic somatostatin dissolved in isotonic saline solution; the initial dose was 25 microgram and a continuous infusion of 2.5 microgram/kg/h was administered thereafter. A decrease in the ulcer index was observed in the rats perfused with somatostatin (p less than 0.01) as well as a decrease in the histamine (p less than 0.001) and serotonin (p less than 0.01) gastric mucosal contents. These effects of somatostatin on restraint-induced stress ulcer in rats are probably to be explained by microcirculatory changes in the gastric mucosa determined by the vasoactive amines (histamine and serotonin). They constitute an important factor in the pathogenesis of these lesions.

Blockage of the ether-induced surge of prolactin by naloxone in male rats.

Department of Physiology, Abramsky Hall, Queen's University, Kingston, Ontario, Canada, K7L 3N6 (Received 17 July 1978) It is well established that the stress of ether anaesthesia raises the level of prolactin in the circulation of the rat (Wakabayashi, Arimura &amp; Schally, 1971; Krulich, Hefco, Illner &amp; Read, 1974). Morphine or the endogenous morphine-like peptides, endorphins and enkephalins, can stimulate the secretion of prolactin in vivo (Ojeda, Harms &amp; McCann, 1974; Martin, Audet &amp; Saunders, 1975; Bruni, Van Vugt, Marshall &amp; Meites, 1977; Rivier, Vale, Ling, Brown &amp; Guillemin, 1977; Chihara, Arimura, Coy &amp; Schally, 1978); naloxone, however, blocks the stimulatory effects of these substances (Bruni et al. 1977; Rivier et al. 1977). It was recently demonstrated that naloxone inhibits the secretion of prolactin induced by stress due to heat or immobilization (Van Vugt, Bruni &amp; Meites, 1978). The restraintinduced stress produced an immediate increase in the concentration of prolactin

Experimental stress ulcers in acidotic and nonacidotic renal insufficiency.

Stress ulcers are a frequent complication in patients with renal insufficiency. Rats were used to study the effect of renal insufficiency on restraint-induced stress ulcer formation. Acidotic, hyperkalemic renal insufficiency produced by the nephrotoxin uranyl nitrate and nonacidotic, normokalemic renal insufficiency produced by partial nephrectomy followed by internal contralateral nephrectomy enhance restraint-induced gastric erosions and ulcers. These studies demonstrate that both acute renal insufficiency with its concomitant acidosis and hyperkalemia and uremia enhance restraint-induced stress ulcer formation, possibly by impairing the normal reparative process of the gastric mucosa.