Isachenko M. Characteristics of left ventricular remodeling markers and nitrogen oxide system state in physiological influences and experimental pathological conditions.

The aim of the study was to find out the pathogenetic mechanisms of nitrogen oxide system effect on left ventricular myocardial remodeling in rats in different conditions (intermittent 15-day and 60-day hypoxia) and hypertension (essential - SHR and endocrine-salt model). To realize that aim, the following objectives were formulated: to study massmetric and morphodensitometric characteristics of cardiomyocytes, the state of the nitrogen oxide system and the marker profile of remodeling in intact Wistar rats; in Wistar rats exposed to 15-day and 60-day long-term intermittent hypoxia; in rats with essential arterial hypertension (SHR) and in Wistar rats with endocrine-salt model of arterial hypertension (ArtH) as well as to determine the pathogenetic features of the heart "geometry" remodeling depending on the nitrogen oxide system state, the etiopathogenetic factor and its impact duration on the cardiovascular system based on the analysis of the results obtained. In the thesis, it has been experimentally proved that myocardial remodeling develops in both physiological and pathological effects on the cardiovascular system, and the profile of remodeling markers and the nitrogen oxide system state are influenced by the etiology and duration of exposure. The informative criteria for the nature of myocardial remodeling in the experiment have been developed, and it has been determined that short-term intermittent hypoxia induces physiological hypertrophic type of myocardial remodeling with increased visco-elastic properties of the heart muscle and decreased cardiomyocyte death. However, prolonged hypoxia results in pathological fibrous-apoptotic type of myocardial remodeling with significant fibrosis, severe hypertrophy, increased myocardial stiffness and massive apoptosis of cardiomyocytes. Experimental ArtH, regardless of etiopathogenetic features, drives pathological myocardial remodeling with model-related differences: in the case of essential – it is the hypertrophic-fibrous type of remodeling with moderate apoptotic rate, in endocrine-salt – hypertrophic-apoptotic type. The pathogenetic role of the nitrogen oxide system in myocardial remodeling in the effects on the cardiovascular system has been substantiated, characterized by an increase in mRNA of all three NOS isoforms with increased plasma concentration of nitrotyrosine in rats. The etiopathogenetic association between changes in the NOS enzyme isoform profile in prolonged hypoxic effects and ArtH has been proved, which leads to a decrease in nitrites levels with an increase in nitrotyrosine.