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In vivo effect of isothiourea derivatives on NO production was studied by the method of electron paramagnetic resonance spectroscopy with a spin trap. We evaluated the influence of these compounds on hemodynamic parameters in anesthetized rats with hypovolemic shock. A correlation was found between the size of S,N-substituents in isothiourea derivatives (methyl, ethyl, and isopropyl) and NO inhibitory activity of compounds. The antihypotensive effect was more pronounced in compounds with high NO inhibitory activity containing the isopropyl radical.

In this work the attempt to estimate a nitric oxide (NO*) role in regulation of the number of pool haemopoietic stem cells at the irradiated mice was made. With this purpose the number of new compounds from dihydrothiazine-thiazoline line was synthesized, their NO-inhibiting activity was investigated in vivo by the method of ESR-spectroscopy of spin trap and their influence on an output endogenous spleen colonies (CFU-S-8) after the total sublethal y-irradiation of mice in a doze of 6 Gy was also investigated. Was shown, that the tested compounds reduced the contents of NO* in a liver tissue of mice which have received an injection of nitric oxide synthesis inductor - lipopolysaccharide, and also increased an output CFU-S-8 forming endogenous colonies in the spleen of the irradiated mice. Received data testify to perceptivity of search radioprotective agents among NO* synthesis inhibitors.

The effect of radioprotectors of different structure on the syntheses of nitric oxide induced by endotoxin in mice was studied. Using ESR-spectroscopy and spin trap techniques, it was shown that compounds of different chemical structure, such as aminothiols, isothiuronium derivatives, thiazolines, indolylalkylamines and others, suppressed the nitric oxide production in a whole body. The analysis of the relevant literature has confirmed the phenomenon described by the authors: radioprotectors show NO-inhibiting activity.

Using the method of electron paramagnetic spectroscopy we demonstrated that thiazine-thiazoline compounds and aminoethyl isothiourea containing the thioamidine group inhibit NO production in the liver of endotoxin-treated mice. Injection of these agents to anesthetized rats increased arterial pressure and enhanced respiration rate. This effect probably reflects inhibition of not only inducible, but also the constitutive synthesis of NO by compounds with thioamidine group.

The method of dose fractionation and decreasing the dose-rate using "macro-" and "microcolonies" techniques was used to study the ability of CFU-S-8 and CFU-S-12 to repair sublethal radiation damages after irradiation thereof within the bodies of bone-marrow donors and recipients. A more committed CFU-S-8 population was found to surpass a younger and less committed CFU-S-12 population with respect to their repairability.

The method of "macro-" and "microcolonies" was used to study the radiosensitivity of CFU-S that form "early" (8 days) and "late" (12 days) splenic colonies after transplantation of syngeneic bone marrow to fatally exposed mice: no significant differences were found. Median lethal doses (D0) for CFU-S-8 and CFU-S-12 were 1.03 and 1.13 Gy for "microtest" and 0.99 and 1.16 Gy for "microtest" respectively.

Dose dependences of heat-induced inactivation of CFUs have been described for the temperature range of 41 to 44 degrees C. The energy of activation of the processes of thermal death was 100-120 kcal/M. CFUs were more resistant to heating than the cells of mouse leukaemia. Heating 1 h or immediately before irradiation had a radiosensitizing effect on CFUs. When bone marrow cells were heated 1 h after irradiation the radiosensitizing effect was absent: there was only a simple summation of the effects of the two damaging agents.