Nitric Oxide as a Factor of Genetically Determined Resistance to Stress Damages and Adaptive Protection

August rats are more resistant to stress-induced gastric damages than Wistar rats. These interstrain differences were abolished after blockade of nitric oxide (NO) synthesis with NO-synthase inhibitor L-NNA, which indicates that NO contributes to genetically determined resistance to stress-induced injuries. Repeated treatment with L-NNA caused gastric ulceration in Wistar, but not in August rats. This is probably related to higher basal production and more intensive accumulation of NO in August rats compared to Wistar rats. Administration of L-NNA during adaptation to hypoxia suppressed its protective effects on the stomach in stress, which indicates that NO acts as the factor of adaptive protection.     

Differences between August and Wistar rats in stress reactions and in the development of adaptation to stress

Control and acutely stressed August rats have corticosterone levels 62% and 15% higher, respectively, than their Wistar counterparts, indicating that the activity of stress-mediating hypothalamic-pituitary-adrenal system in August rats is higher. On the other hand, the intensity of stress reactions and, consequently, the degree of activation of this system in August rats are 40–50% lower, as is the blood level of creatine phosphokinase. During adaptation to stress, August and Wistar rats show a similar decrease in the stress reaction and in its damaging effects. However, judging from the blood corticosterone/insulin ratio, adaptation to stress in August rats coincides with intensification of catabolic processes and a reduction in the efficiency of energy production. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 8, pp. 156–159, August, 1996     

Adaptation to stress improves resistance to gastric damage during acute stress in Wistar rats and decreases resistance in August rats: role of serotonin

In August rats more resistant to acute stress-induced gastric damage than Wistar rats, preadaptation to nondamaging stress exposure did not prevent damage and even potentiated these damages. By contrast, in Wistar rats such adaptation decreased gastric damage caused by acute stress. Higher initial resistance of August rats to stress damage was associated with higher serotonin level and lower norepinephrine/serotonin ratio in the gastric mucosa than in Wistar rats. The negative effect of adaptation in August rats was associated with decreased serotonin level and increased norepinephrine/serotonin ratio in the stomach during stress. In Wistar rats exposed to stress the protective effect of adaptation was associated with an increase of serotonin content and a decrease of the norepinephrine/serotonin ratio in the stomach. Hence, the degree of resistance to stress-induced gastric damage can be due to genetically determined serotonin level and norepinephrine/serotonin ratio in the stomach.     

Melatonin and ulceration in rat stomach in acute emotional stress

Formation of peptic ulcers under conditions of acute emotional stress was studied in rats injected with different doses of melatonin (0.5, 1, and 2 mg/kg). The number of total length of peptic ulcers increases under conditions of stress. In unstressed rats melatonin induces ulceration of gastric mucosa. In a dose of 1 mg/kg melatonin exerts protective effect on gastric mucosa. No significant changes in the number and total length of peptic ulcers are noted with 0.5 and 2 mg/kg melatonin. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 1, pp. 12–14, January, 1998     

Effect of interleukin-1β on platelet aggregation in August, Wistar, and WAG rats in acute emotional stress

Acute emotional stress inhibits platelet aggregation in August and WAG rats and reduces it in Wistar rats. Functional parameters of platelets are altered predominantly in passive rats. Interleukin-1β reduces the rate of platelet aggregation in nonstressed August and WAG rats and elevates it in Wistar rats. Preliminary injection of interleukin-1β reduces the stress-induced changes in platelet aggregation in August and WAG rats; while in Wistar rats this effect is not observed. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 8, pp. 144–147, August, 1997     

Catecholamines in the adrenals of August and Wistar rats with acute emotional stress

Acute emotional stress caused by immobilization and cutaneous electrical stimulation increases the relative weight of adrenals in Wistar rats and decreases it in August rats. The epinephrine and norepinephrine contents of the adrenals in control and stressed August rats are higher than in Wistar rats. Acute stress lowers the levels of these biogenic amines in the adrenals of both strains, particularly in Wistar rats. The left adrenal gland of control and stressed August rats, but not of Wistar rats, has a higher content of biogenic amines than the right, and both adrenals of stressed August rats contained higher dopamine concentrations than those of stressed Wistar rats. Presumably, epinephrine and norepinephrine are resynthesized in the adrenals of stressed August rats at higher rates than they are released from these glands, while the adrenals of Wistar rats respond to stress by rapidly releasing these catecholamines and resynthesizing them at a slow rate. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 123, No. 6, pp. 645–648, June, 1997     

Synthesis of HSP70 in blood leukocytes as a marker of stress resistance during adaptation

The effect of preadaptation to non-damaging emotional stress on the synthesis of HSP70 (stress-limiting factor) in peripheral blood leukocytes was studied in experiments on August and Wistar rats characterized by different sensitivity of the gastric mucosa to stress-induced injury. It was found that preadaptation improves stress resistance of Wistar rats characterized by lower innate resistance to acute mental stress and activates HSP70 synthesis in blood leukocytes. In August rats characterized by higher resistance to acute stress, adaptation reduced the resistance to stress-induced injuries, which was accompanied by the absence of activation of HSP70 synthesis in leukocytes compared to the level observed in nonadapted rats during acute stress. Thus, the intensity of HSP70 synthesis in peripheral blood leukocytes can serve as a marker of changes in animal resistance to acute stress caused by adaptation to non-damaging stress exposures and probably to other environmental factors. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 12, pp. 613–616, December, 2007     

Antiulcerogenic effects of benzylpenicillin in acutely stressed rats

The antibiotic benzylpenicillin was found to produce dose-dependent antiulcerogenic effects in rats when administered immediately before their exposure to acute stress (swimming for 1 h) that led to gastric mucosal ulceration. Such effects were not observed in rats given benzylpenicillin 48 h before stress exposure. The results of this study suggest that in acutely stressed animals benzylpenicillin may activate as yet unidentified mechanisms which afford protection to the gastric mucosa and which are not associated with the longer-lasting antimicrobial effects of this antibiotic. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 8, pp. 131–133, August, 1994     

Ulcerative gastric lesions in august and wistar rats: Effects of acute emotional stress

Wister rats, but not August rats, developed ulcerative lesions in the gastric mucosa as a results of exposure to severe emotional stress caused by immobilization in closed tubes submerged in water. In addition, the stressed rats of both strains showed an increased ratio of thymus weight and a decreased ratio of adrenal weight to body weight. It is concluded that emotionally stressed Wistar, but not August, rats are prone to develop ulcerative gastric lesions. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 11, pp. 469–470, November, 1995 Presented by K. V. Sudakov, Member of the Russian Academy of Medical Sciences)     

Gastric mucosal lesions caused in rats of different strains by emotional stress,and the protective effect of interleukin 1β

Acute emotional stress results in damage to gastric mucous membranes in August, Wag, and particularly Wistar rats. The damage is less severe in rats preinjected with inter-leukin 1β into a lateral ventricle of the cerebrum. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 3, pp. 238–239, March, 1994     

Protein content in rat brain neurons predisposed and resistant to emotional stress

Protein content was measured by interferometry in the cerebral neurons of August rats predisposed to emotional stress and Wistar rats resistant to it. Protein content was 16–18% lower in the neurons of the third and fourth layers of the sensorimotor cortex and 51% higher in the caudate nucleus neurons (cerebral subcortical nodes) of August rats than in Wistar rats. This indicates an inversion in protein distribution in the cortex and subcortex of August rats which are characterized by typical protein content in different types of neurons and apparently by peculiar cerebral structure and function. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 10, pp. 477–480, October, 1998     

Effects of different stress techniques and adaptation on behavioral and somatic indices in rats

We developed a model of stress (free swimming in a cage) which allows to assess the immediate and long-term effects of emotional stress. This stress induced typical changes in the open field test and ulceration of gastric mucosa. Unlike standard immobilization stress the proposed technique excludes a traumatic factor, it is well reproducible and simple. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 8, pp. 157–160, August, 1999     

Comparative analysis of polypeptides in the heat shock proteins synthesized in the myocardium of Wistar and August rats

The use of two-dimensional electrophoresis to study the polypeptide composition of heat shock proteins 70 synthesized in the myocardium of Wistar and August rats in response to thermal stress and repetitive immobilization stress revealed interstrain differences in the composition of stimulated polypeptides in these proteins. The differences are mainly due to differential expression of the heat shock protein gene(s) encoding polypeptides with pI 6.2–6.0 in the two strains. The drastically reduced levels of the synthesis and/or accumulation of some heat shock proteins 70 in the hearts of August rats are associated with their failure to develop cardioprotective phenomena in response to repetitive immobilization stress. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 7, pp. 30–32, July, 1995 Presented by R. S. Karpov, Member of the Russian Academy of Medical Sciences     

Emotional state and one-trial learning in OXYS rats with hereditarily elevated production of oxygen radicals

Comparative analysis of unconditioned and conditioned behavior of Wistar and prematurely aging OXYS rats revealed that the latter have significantly reduced locomotor and exploratory activities, increased anxiety in the elevated plus-maze test, spatial disorientation, and abnormal associative learning. OXYS rats can be used as a biological model for studying molecular, neurobiological, and neurochemical mechanisms of brain aging. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 8, pp. 155–158, August, 2000     

Lipid peroxidation and antioxidant enzymes in the brain of rats exposed to acute emotional stress: Effect of interleukin-1β

Acute emotional stress is shown to raise the level of malonic dialdehyde in the hypothalamus of August rats. After intraventricular administration of interleukin-1β, the malonic dialdehyde level and the activity of antioxidant enzymes tended to rise selectively in the hypothalamus (but not in the sensorimotor cortex) of August, Wistar, and WAG rats. In the presence of this interleukin, acute emotional stress did not cause increases in lipid peroxidation products in the hypothalamus of August rats. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 9, pp. 244–247, September, 1995     

Plasma and lymph electrolyte and endocrine parameters in rats with genetically-determined arterial hypertension

Hemolymphatic interactions of electrolytes and plasma contents of aldosterone and insulin are studied in rats with genetically-determined stress-induced arterial hypertension (NISAG) and in normotensive rats (Wistar). Correlation analysis shows that alterations in electrolyte metabolism in NISAG are strongly determined by endocrine influences. These alterations are regarded, on the one hand, as a mechanism responsible for generically-determined arterial hypertension, and, on the other hand, as a variant of “adaptation disease” accompanied by transformation of primarily adaptive reactions into a pathogenic factor of arterial hypertension. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 7, pp. 36–38, July, 1997     

Morphofunctional characteristics of connective tissue in emotionally stressed august and wistar rats

August rats, which are predisposed to emotional stress, are shown to differ from Wistar rats, which are not so predisposed, in the morphofunctional organization of lymphoid and connective tissues. In August as compared to Wistar rats, the lymphoid tissue of the spleen, trachea, bronchi, intestine, and lymph nodes is less abundant, the pancreatic insular apparatus is developed much better, and loose connective tissue contains more mast cells without signs of degranulation. Emotional stress leads, in both strains, to strong connective tissue congestion, massive hemorrhages, edema of loose connective tissue in the renal medullary substance and in the liver, focal or focal/confluent connective tissue metachromasia, and progressive mast cell degranulation. These changes are all more pronounced in August rats. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 6, pp. 571–573, June, 1995     

Effect of interleukin-1β on the thymus, adrenals, and spleen in august, wistar, and WAG rats in stress

Emotional stress causes a decrease in the relative mass of the thymus, adrenals, and spleen in August, Wistar, and WAG rats, which is the greatest in animals with a low motor activity in the open field test. Intraventricular administration of interleukin-1β diminishes the decrease in the relative mass of spleen in August and Wistar rats, has no significant effect on the relative mass of thymus in all rats, and leads to an increase in the relative mass of adrenals in immobilized WAG rats. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 7, pp. 32–35, July, 1997     

Synthesis of heat shock proteins (HSP70) in blood leukocytes as a criterion of the resistance to stress injury

The resistance of August rats to ulceration of the gastric mucosa induced by acute emotional stress was higher than in Wistar rats. August rats exhibited not only more potent activation of the protective nitric oxide system and mobilization of the immune system, but also increased synthesis of cytoprotective heat shock proteins HSP70 in blood leukocytes under stress conditions. Our results indicate that HSP70 protein synthesis in blood leukocytes during stress reflects organism’s resistance to stress and, probably, to other adverse factors. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 142, No. 12, pp. 614–617, December, 2006     

Is nitric oxide involved in the adaptation to the stress-induced damage?

The iron dinitrosyl complex (a NO donor), adaptation to stress, and their combination suppress the stress-induced ulcer formation. Nω-nitro-L-arginine, a NO synthetase inhibitor, reduce the antistress effect of adaptation. Severe stress induces a sharp decrease in the NO production in the liver and brain. After adaptation to stress, the NO production in the liver and brain does not differ significantly from control levels. However, adaptation attenuates a decrease in the NO production in the liver caused by severe stress. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 9, pp. 274–277, September, 1998