ACTIVITY MODULATION OF VARIOUS NITRIC OXIDE SYNTASES AS AN APPROACH TO ENDOTHELIAL DYSFUNCTION THERAPY

Abstract

Nitric oxide as a therapeutic approach to the treatment of cardiovascular diseases attracted the attention of researchers at the end of the 19th century. As a vasodilator, nitric oxide may be a unique therapeutic agent for the treatment of hypertension and, as a result, renal failure and left ventricular hypertrophy.The aim of the article is to analyze the literature data on possible ways of modulating the activity of various nitric oxide synthases as an approach to the treatment of endothelial dysfunction.Materials and methods. When searching for materials for writing a review article, such abstract databases as PubMed, Google Scholar, e-Library, etc., were used. The search was carried out on the publications for the period from 1990 to 2021. The following words and phrases were chosen as parameters for the literature selection: nitric oxide; NO synthase; endothelial dysfunction; NO synthase activator; NO synthase inhibitor.The following words and phrases were chosen as parameters for the literature selection:Results. The article presents the history of the nitric oxide discovery and its biological role, the process of its biosynthesis, as well as the isoforms of its synthesizing enzymes (NOS): neuronal – nNOS, endothelial – eNOS and inducible iNOS, and their role in normal and pathological physiology. The process of NOS uncoupling (its molecular mechanisms) has been considered as the basis of endothelial dysfunction.The examples of the pharmacological correction (BH4, arginase inhibitors, statins, resveratrol) are presented. In addition, NO synthase activators (calcium dobesilate, cavNOxin, and some NOS transcription activators), as well as non-selective (L-NMMA, 1-NNA, L-NAME, ADMA, 546C88, VAS203) and selective (L-NIO, 7-nitroindazole, aminoguanidine, L-NIL, GW273629, GW274150, cavtratin) inhibitors of nitric oxide synthasehave been described.Conclusion. Nitric oxide synthases continue to be promising targets for the development of agents that modulate their activity to correct various pathologies. As a therapeutic approach, modulation of the nitric oxide synthase activity can be implemented to treat endothelial dysfunction, which is the cause for complications of many diseases.