Involvement of endothelial NO synthase expression regulators in the mechanisms of endothelial dysfunction development against the background of cobalt chloride and L-NAME exposure in experiment

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Dzugkoev Sergey Gavrilovich, Dzugkoeva Fira Solomonovna, Margieva Olga Ivanovna, Mozhaeva Irina Viktorovna


Literature representations about the toxicity of heavy metals, one representative of which is cobalt, are not exhaustive. Insufficient attention is paid to the violation of nitroxide-producing endothelial function as a risk factor for vascular complications. The aim of the study was to investigate the characteristics of the effect of cobalt chloride and its complex with L-NAME on indicators of LPO system - AOS, NO-producing function of the endothelium, including the expression of endothelial NO synthase. To realize the goal, experimental studies were conducted on Wistar rats with exogenous load of cobalt chloride and its combination with endothelial NO synthase inhibitor - L-NAME. The following parameters were determined in the experiment: malondialdehyde concentration, catalase activity and ceruloplasmin concentration, nitric oxide content, and the level of endothelial NO synthase expression. The data showed a significant increase in oxidants in the body and their ability to inhibit the production of nitric oxide (NO), the main vasodilator. Against the background of combined administration of cobalt chloride and L-NAME revealed even greater activation of free-radical reactions, more pronounced inhibition of nitric oxide formation. When administering cobalt and modified L-arginine, there is a violation of the internal molecular structure of endothelial NO synthase (eNOS) and the ability of the enzyme to produce active oxygen metabolites (AMCs). In contrast, L-arginine stimulates the expression level of eNOS, the formation of nitric oxide and inhibits lipoperoxidation. This type of research is highly relevant because only knowledge of the mechanisms of endothelial dysfunction will allow a predictive approach to preventive measures.

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