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Metabolic profile of blood serum in experimental arterial hypertension
A A Seryapina1, A A Malyavko1, Yu K Polityko1
1Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia.
Insights
Metabolomic profiling reveals distinct blood serum differences in stress-induced hypertension models. These findings in ISIAH rats highlight key metabolites linked to glucose metabolism, nitric oxide, and inflammation, aiding personalized hypertension treatment.
Area of Science:
- Biochemistry
- Physiology
- Genetics
Background:
- Essential hypertension involves complex interactions between multiple body systems.
- Genetic and environmental factors contribute to hypertension's heterogeneous nature.
- Experimental models, like the ISIAH rat, are crucial for studying primary hypertension.
Purpose of the Study:
- To analyze the blood serum metabolic profile of male ISIAH rats with genetic stress-dependent arterial hypertension.
- To compare metabolic profiles with normotensive WAG rats to identify hypertension-specific markers.
- To explore the link between identified metabolites and hypertension pathogenesis.
Main Methods:
- Utilized metabolomics and nuclear magnetic resonance (NMR) spectroscopy.
- Analyzed blood serum samples from ISIAH and WAG rats.
- Identified 56 metabolites, with 18 showing significant interstrain differences.
Main Results:
- Hypertensive ISIAH rats exhibited higher levels of leucine, isoleucine, valine, myo-inositol, glutamate, glutamine, ornithine, and creatine phosphate.
- Lower concentrations of 2-hydroxyisobutyrate, betaine, tyrosine, and tryptophan were observed in ISIAH rats.
- Metabolite alterations correlated with dysregulated glucose metabolism, nitric oxide synthesis, catecholamine pathways, and inflammation.
Conclusions:
- Metabolic profiling provides insights into the pathogenesis of stress-dependent arterial hypertension.
- Specific metabolite ratios are associated with key physiological changes in hypertension.
- These findings support a personalized approach to hypertension prevention and treatment.
Abstract:
The etiology of essential hypertension is intricate, since it employs simultaneously various body systems related to the regulation of blood pressure in one way or another: the sympathetic nervous system, renin-angiotensin-aldosterone and hypothalamic-pituitary-adrenal systems, renal and endothelial mechanisms. The pathogenesis of hypertension is influenced by a variety of both genetic and environmental factors, which determines the heterogeneity of the disease in human population. Hence, there is a need to perform research on experimental models - inbred animal strains, one of them being ISIAH rat strain, which is designed to simulate inherited stress-induced arterial hypertension as close as possible to primary (or essential) hypertension in humans. To determine specific markers of diseases, various omics technologies are applied, including metabolomics, which makes it possible to evaluate the content of low-molecular compounds - amino acids, lipids, carbohydrates, nucleic acids fragments - in biological samples available for clinical analysis (blood and urine). We analyzed the metabolic profile of the blood serum of male ISIAH rats with a genetic stress-dependent form of arterial hypertension in comparison with the normotensive WAG rats. Using the method of nuclear magnetic resonance spectroscopy (NMR spectroscopy), 56 metabolites in blood serum samples were identified, 18 of which were shown to have significant interstrain differences in serum concentrations. Statistical analysis of the data obtained showed that the hypertensive status of ISIAH rats is characterized by increased concentrations of leucine, isoleucine, valine, myo-inositol, isobutyrate, glutamate, glutamine, ornithine and creatine phosphate, and reduced concentrations of 2-hydroxyisobutyrate, betaine, tyrosine and tryptophan. Such a ratio of the metabolite concentrations is associated with changes in the regulation of glucose metabolism (metabolic markers - leucine, isoleucine, valine, myo-inositol), of nitric oxide synthesis (ornithine) and catecholamine pathway (tyrosine), and with inflammatory processes (metabolic markers - betaine, tryptophan), all of these changes being typical for hypertensive status. Thus, metabolic profiling of the stress-dependent form of arterial hypertension seems to be an important result for a personalized approach to the prevention and treatment of hypertensive disease.
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