Fragments of extracellular DNA are permanently released into the blood flow due to cell apoptosis and possible de novo DNA synthesis. To find out whether extracellular DNA can affect the synthesis of nitric oxide (NO), one of key vascular tone regulators, we studied in vitro effects of three artificial DNA probes with different sequences and 10 samples of extracellular DNA (obtained from healthy people and patients with hypertension and atherosclerosis) on NO synthesis in endothelial cell culture (HUVEC). For detection of NO in live cells and culture medium, we used a NO-specific agent CuFL penetrating into the cells and forming a fluorescent product FL-NO upon interaction with NO. Human genome DNA fragments affected the content of NO in endothelial cells; this effect depended on both the base sequence and concentration of DNA fragments. Addition of artificial DNA and extracellular DNA from healthy people into the cell culture in a low concentration (5 ng/ml) increased the detected NO concentration by 4-fold at most. Cytosine-guanine (CG)-rich fragment of the transcribed sequence of ribosomal repeat was the most powerful NO-inductor. The effect of DNA fragments on NO synthesis was comparable with that of low doses of oxidizing agents, H(2)O(2) and 17β-estradiol. Extracellular DNA samples obtained from patients with hypertension and atherosclerosis decreased NO content in cells and medium by 1.3-28 times compared to the control; the effect correlated with the content of CG-rich sequences.

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The aims of the present work were to perform a comparative study of the effects of delta sleep-inducing peptide and Deltaran on neurons in emotiogenic brain structures and to address the question of whether it is possible to prevent or decrease the negative influences of stress loads on the severity of subsequent cerebral ischemia in rats, using glycine with delta sleep-inducing peptide combined in the neuroprotective formulation Deltaran. The results showed that Deltaran and delta sleep-inducing peptide had largely the same actions on the nature of spike activity of neurons in the dorsal hippocampus, paraventricular nucleus of the hypothalamus, and ventral anterior nuclei of the thalamus, evoking activation of some of the neurons in these brain structures. The dorsal hippocampus was dominated by activation of spike activity in response to administration of delta sleep-inducing peptide; Deltaran produced activation mainly in the paraventricular nuclei of the hypothalamus. In all animals given Deltaran, the index of brain blood supply was significantly greater than in animals not given Deltaran. The survival rate of cerebral ischemia was 100% in animals given Deltaran. Death occurred in 38% of animals not given Deltaran.