Elucidation of the molecular basis of various diseases and pathological states of human organism is one of the most significant problems of medicine and biology. It is known, that the ways of production of free radicals of oxygen and nitric oxide are closely binded. The synthesis of nitric oxide over standard level may cause nitrosative stress, that is binded with active forms of nitric oxide, for example, peroxinitrite and nitric dioxide. The formation of nitrosothiols is one of the markers of nitrosative stress also.

Given that under some diseases erythrocytes are involved in pathological process the aim of the present work was to study the indexes of the system of nitric oxide synthesis and nitrosylation in erythrocytes of patients with cardiomyopathy.

The materials for the study were the erythrocytes of healthy subjects (control group) and patients with dilatated cardiomyopathy (20 patients, at the age from 47,0 to 53,0 years). The blood was taken in Simferopol Cardiological Centre before treatment for an illness. The erythrocytes were hemolisated by distilled water. In hemolisates of erythrocytes was determined the content of NO-anions (NO2 – and NO3–), low-molecular and high-molecular products of nitrosylation and the activity of arginase, cNOS and iNOS.

For study all indexes were utilizated spectrophotometric methods of biochemical analysis. It has been shown that in erythrocytes of patients with dilatated cardiomyopathy the system of nitric oxide synthesis is changed. The metabolism of L-arginine by arginase prevails over oxidative metabolism with NO-synthesis (was 100% higher as compared with control group). The activity of Ca2+-independent nitric oxide synthase was increased (33% higher as compared with control group) and the activity of Ca2+-dependent NOsynthase was lowered (70% less as compared with control group). The accumulation of NO-anions in erythrocytes of patients was limited. The level of NO2– and NO3–-anions was less as compared with control group (24,6% and 49,3%, accordingly). The level of low-molecular products of nitrosylation was 46,8% less as compared with control group.

It is known, that nitrosoglutatione is one of the main low-molecular products of nitrosylation. The lowering of the content of low-molecular products of nitrosylation in erythrocytes of patients with dilatated cardiomyopathy may be as index of releasing of glutatione from processes of nitrosylation for more active utilization in reductative reactions.

At the same time the content of high-molecular products of nitrosylation was increased (133,7% higher as compared with control group). So far as the high-molecular products are, in the main, nitrosylated proteins, these changes in erythrocytes of patients with dilatated cardiomyopathy may have certain influence on structural-functional state of erythrocyte proteins, in particular, of haemoglobin. It is known that NO may compete with oxygen for bond with haem iron. It this connection, the nitrosylation of iron in haemoglobin molecule may have influence on oxygenation process.

The changes that are observed in the system of nitric oxide synthesis in erythrocytes of patients with dilatated cardiomyopathy may have influence on generation of nitric active forms and level of reductated glutatione also.

The rising of the level of high-molecular products of nitrosylation is evidence that in erythrocytes of patients with dilatated cardiomyopathy the nitrosative stress is developed. At the same time, the lowering of the level NO-anions and the level of low-molecular products of nitrosylation is evidence that in erythrocytes of patients some compensative reactions are realized.

Thus, under dilatated cardiomyopathy the changes in the nitric oxide metabolism in erythrocytes are accompanied with the development of nitrosative stress and realization of some compensative reactions.

Ключові слова: erythrocytes, system of nitric oxide synthesis, NO-synthases, NO-anions, low-molecular and high-molecular products of nitrosylation, dilatated cardiomyopathy

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