STUDY FOR THE EFFECT OF K-8 COMPOUND ON THE RATS RESISTANCE TO IMMOBILIZATION AND NOCICEPTIVE STRESS INFLUENCE IN THE SETTING OF NO-SYNTHASES BLOCKING

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In the setting of stress, a significant augmentation of hormones concentration (catecholamines, glucocorticoids etc) in blood leads to the development of various pathological conditions, including hypertension, cardiac arrhythmias, decreased myocardial contractility, etc. Adverse effects of excessive activation of stress implementing systems are modulated with stress-limiting, the principal one of which is the system of nitric oxide. In this regard, it seems promising the creation and development of new agents to limit the stress myocardial damage which affects a NO-ergic system. Purpose of this work was to investigate the influence of (4-bromophenyl) ethylidene hydrazide 2- [6-methyl-1-(thiethanes-3-yl) uracil-3-yl] acetic acid, a compound with a laboratory code K-8, on the animals resistance to 24 hour immobilization and nociceptive stress influence in the conditions of NO synthesis blocking. Materials and methods of the study: the runs involved outbred female rats weighed 200-250 g. Stress was modeled by the hanging up of an animal for the dorsal skin neck fold for 24 hours. We have formed 5 groups: 1) intact animals (n=8); 2) stressed female rats which were given with a physiological solution (n=8); 3) stressed animals which were given with the compound under study at dose of 15 mg/kg (n=5) and 5) stressed female rats which were given with L-NAME and the compound under study (n=8). All the substances were injected abdominally before and after the 12 hours of hanging up. Arterial tension was measured with the use of noninvasive measurer Kent Scientific Corporation (Canada). Results: we have found that the blocking of nitric oxide synthesis leads to the reduction of animal resistance to stress. After 24-hour immobilization nociceptive stress 7 of 9 rats treated with L-NAME (77.8%) died. The group of rats treated with K-8 substance 3 of 8 female rats died in the setting of NO deficiency (37.5%) (p≤0.05). This showed the stress resistance augmentation with the effect of the compound under study. There were no deaths observed in the intact animals, stressed females in the control group, and rats subjected to emotional stress in the setting of injection of the K-8 compound. In the group of stressed rats form the control group AT increased after 24 hours of stress exposure by 7.4% compared with the original data (p≤0.05), whereas intact female rats figure decreased by 7.3%. In stressed animals, which were given with a compound under study, AT did not changed compared with the outcome of the original level. Arterial tension was not measured in the only one survived rat which was given with L-NAME. The group of animals treated with K-8 compound had AT decreased by 5.8% concerning the original level in the setting of NO-synthases blocking. This index was significantly lower than the index of the stressed rats (p≤0.05), which probably indicates the ability of the test compound to level the failure of adaptation processes due to the lack of NO. Conclusions: K-8 compound increases the resistance of animals to immobilization nociceptive stress in the condition of NO-synthases blocking.