The dissertation is devoted to elucidating the role of the nitric oxide (NO) system in the non-pregnant and pregnant mice BALB/c with antiphospholipid syndrome and biochemical mechanisms of protective action of nitric oxide modulators in brain, liver and kidney in this pathology. The expediency of using the precursor of NO, L-arginine, in combination with a inhibitor of the inducible isoform of nitrogen oxide
synthase, aminoguanidine, in order to correct the identified violations of the studied processes in antiphospholipid syndrome has been experimentally substantiated. It was found that in the non-pregnant and pregnant animals with antiphospholipid syndrome there is a relative lack of NO induced by endothelial NO-synthase, against the background of general hyperproduction of NO, which is synthesized under the influence of inducible NO-synthase. The experimental antiphospholipid syndrome is accompanied by the development of endothelial dysfunction, hypercoagulation, activation of apoptosis and decreased production of reactive oxygen species in blood leukocytes, imbalance of pro- and
anti-inflammatory cytokines, reactive astrogliosis, oxidative and nitrooxidative stress, and disorders of tissue respiration in the brain, liver and kidneys. It was found that the precursor of NO, L-arginine, in the non-pregnant and pregnant mice with antiphospholipid syndrome promotes the activation of eNOS in the blood and liver, accompanied by increased bioavailability of NO in the cerebellum, cerebral hemispheres, liver and kidneys. It is shown that during introduction of L-arginine there is an improvement of ultrastructural disorders of the vessels of the microcirculation of the liver and normalization of the number of circulating desquamated endothelial cells. It was found that L-arginine under
the conditions of APS reduces the appearances of hypercoagulation, helps to normalize the viability of leukocytes and reactive oxygen species in granulocytes and agranulocytes, and reduces the content of caspase-3 and β-actin in the liver. The effect of L-arginine on the development of oxidative stress in the non-pregnant and pregnant mice with antiphospholipid syndrome is accompanied by inhibition of the activity of membrane lipid peroxidation in the cerebral hemispheres, liver, kidneys; activation of the antioxidant defense system in the cerebral hemispheres, liver, kidneys; normalization of energy supply processes in the liver and kidneys. The effect of L-arginine on the state of the structures of the central nervous system (cerebellum and cerebral hemispheres) in experimental antiphospholipid syndrome before pregnancy and during pregnancy is accompanied by inhibition of reactive astrogliosis, activation of remyelination processes. L-arginine under the conditions of APS exhibits antioxidant, hepato- and nephroprotective properties.
