Urine metabolic profile in rats with arterial hypertension of different genesis

The diversity of pathogenetic mechanisms underlying arterial hypertension leads to the necessity to devise a personalized approach to the diagnosis and treatment of the disease. Metabolomics is one of the promising methods for personalized medicine, as it provides a comprehensive understanding of the physiological processes occurring in the body. The metabolome is a set of low-molecular substances available for detection in a sample and representing intermediate and final products of cell metabolism. Changes in the content and ratio of metabolites in the sample mark the corresponding pathogenetic mechanisms by highlighting them, which is especially important for such a multifactorial disease as arterial hypertension. To identify metabolomic markers for hypertensive conditions of different origins, three forms of arterial hypertension (AH) were studied: rats with hereditary AH (ISIAH rat strain); rats with AH induced by L-NAME administration (a model of endothelial dysfunction with impaired NO production); rats with AH caused by the administration of deoxycorticosterone in combination with salt loading (hormone-dependent form - DOCA-salt AH). WAG rats were used as normotensive controls. 24-hour urine samples were collected from all animals and analyzed by quantitative NMR spectroscopy for metabolic profiling. Then, potential metabolomic markers for the studied forms of hypertensive conditions were identified using multivariate statistics. Analysis of the data obtained showed that hereditary stress-induced arterial hypertension in ISIAH rats was characterized by a decrease in the following urine metabolites: nicotinamide and 1-methylnicotinamide (markers of inflammatory processes), N- acetylglutamate (nitric oxide cycle), isobutyrate and methyl acetoacetate (gut microbiota). Pharmacologically induced forms of hypertension (the L-NAME and DOCA+NaCl groups) do not share metabolomic markers with hereditary AH. They are differentiated by N,N-dimethylglycine (both groups), choline (the L-NAME group) and 1-methylnicotinamide (the group of rats with DOCA-salt hypertension).