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The effect of delta sleep-inducing peptide (DSIP) on the lymphoid structures of small intestine, was investigated. Studies were conducted on 42 male Wistar rats, which were previously assessed in an "open field" test. According to the results of the test, rats were divided into behaviorally active animals (prognostically resistant to stress) and passive ones (resistant to the effects of stress). As a stress, immobilization of the animals in pens with an electrical stimulation of their back for 1 hour, was used. Intraperitoneal injection of DSIP resulted in a reduction of eosinophil number in rats of all the experimental groups. After DSIP injection to the active rats of the control group, the increase in small and medium lymphocyte numbers was detected that was more expressed than in the passive rats. After an acute exposure of behaviorally active rats to stress, the number of the cells of lymphoid series was increased,mainly due to the increase in small and medium lymphocytes. In the group of passive rats, stress exposure and DSIP injection resulted in the increase of plasma cell number in all the duodenal mucosa structures studied.

An aim of the present study was a comparative investigation of a delta-sleep inducing peptide and the drug deltaran on the neural activity of the brain structures involved in emotional processing. Another goal was to analyze the possibility to prevent negative effects of emotional stress on brain ischemia using, along with deltaran, glycine and a delta-sleep inducing peptide. Deltaran and the delta-sleep inducing peptide exert in general similar effect on the burst activity of neurons in the dorsal hippocampus, hypothalamic paraventricular nucleus and ventral anterior thalamic nucleus, inducing amplification of the majority of recorded units. The activation of neuronal activity was seen mostly after the delta-sleep inducing peptide microiontophoresis in the dorsal hippocampus and after the deltaran application in the hypothalamic paraventricular nuclei. The index characterizing blood supply was significantly higher in all rats receiving deltaran as compared to the controls. Animals receiving deltaran survived experimental brain ischemia in 100% cases versus 38% in those not exposed to this drug.

Local cerebral blood flow in the left hemisphere decreased most significantly in low-resistant Wistar rats preexposed to emotional stress. Deltaran selectively increased blood flow in the left hemisphere and improved blood supply to neuronal activity unit of the brain in these animals. This drug prevented progressive decrease in local cerebral blood flow in both hemispheres during the acute stage of ischemia. The effect of Deltaran was related to modulation of collateral blood flow and adequate blood supply to neuronal activity unit in the brain tissue. Deltaran decreased the mortality rate (by 62%) and alleviated the symptoms of cerebral ischemia. The positive effect of Deltaran was more pronounced in the left hemisphere.

Dynamics of the hypokinesia-induced changes of free radical and malonic dialdehyde content in brain, the changes of respiratory chain state and superoxide dismutase activity in liver of rats has been studied using ESR technique and biochemical methods. The effect of the preliminary injection of DSIP and its analogue ID-2 on these dynamics has also been studied. Using a model system constants of the interaction between DSIP or ID-2 and O2-. have been determined. The data point to the antioxidant effect of the administration of the peptides before hypokinesia. This suggests that the effect involves in mechanisms of the anti-stress action of these peptides.

The influence of the delta-sleep inducing peptide (DSIP, 60 and 120 nmol/kg, intraperitoneally) on the content of substance P (SP) in rats hypothalamus was studied on males of August line. DSIP administration significantly increased the mean SP content in the hypothalamus and also its content in animals, stable and predisposed to emotional stress. Daily DSIP administration before putting the rats in conditions of stress increased the SP content in the hypothalamus decreased at the emotional stress. Preliminary single DSIP administration to the animals subjected to stress also increased the SP content. Single DSIP administration in a dose of 60 nmol/kg sharply reduced classical stress manifestations, such as hypertrophy of adrenals and thymus involution.

In acute and chronic animal (rabbits, rats) experiments it has been shown that delta-sleep producing peptide (DSPP) exerts a noticeable effect on the cardiac function and regulation. DSPP at a dose of 60 nm/kg can prolong the effects of vagus and inhibit those of sympathetic nerves on the cardiac function and, consequently, can influence the function of choline- and adrenergic transmitters. DSPP blocks pressor vascular reactions in response to direct electrical stimulation of ventromedian hypothalamus and thus increases the survival of animals exposed to an acute emotional stress. DSPP normalizes the electrical stability of the heart and produces an antiarrhythmic effect on ventricular ectopic beats that occur in response to emotional stresses. In view of this, DSPP can be recommended for clinical trials as a drug preventing cardiac arrhythmias in stressful situations.

In chronic experiments on rabbits, a delta-sleeping inducing peptide was tested for effects on the cardiac electric stability and onset of ventricular premature beats during experimental emotional stress. The peptide in a dose of 60 nm/kg was found to normalize the thresholds of ventricular fibrillation and its predictors and to decrease or abolish spontaneous ventricular premature beats occurring during the stress. This suggests that the delta-sleep-inducing peptide may be used to prevent cardiac arrhythmias during stresses.

The experiments on C57Bl mice with metastatic Lewis lung carcinoma have shown that peptide delta-sleep (DSIP) lowers the stimulation of metastatic spreading which is observed in combination of the surgical removal of the tumour with the emotional-painful stress. The antimetastatic effect is accompanied by stabilization of neurohumoral indices, by a decrease in the intensity of lipid peroxidation and of the acid cathepsin activity in the blood vessels and in the lung tissue.