Abstract
BackgroundThe development of essential hypertension is associated with a wide range of mechanisms. The brain stem neurons are essential for the homeostatic regulation of arterial pressure as they control baroreflex and sympathetic nerve activity. The ISIAH (Inherited Stress Induced Arterial Hypertension) rats reproduce the human stress-sensitive hypertensive disease with predominant activation of the neuroendocrine hypothalamic-pituitary-adrenal and sympathetic adrenal axes. RNA-Seq analysis of the brain stems from the hypertensive ISIAH and normotensive control WAG (Wistar Albino Glaxo) rats was performed to identify the differentially expressed genes (DEGs) and the main central mechanisms (biological processes and metabolic pathways) contributing to the hypertensive state in the ISIAH rats.ResultsThe study revealed 224 DEGs. Their annotation in databases showed that 22 of them were associated with hypertension and blood pressure (BP) regulation, and 61 DEGs were associated with central nervous system diseases. In accordance with the functional annotation of DEGs, the key role of hormonal metabolic processes and, in particular, the enhanced biosynthesis of aldosterone in the brain stem of ISIAH rats was proposed. Multiple DEGs associated with several Gene Ontology (GO) terms essentially related to modulation of BP were identified. Abundant groups of DEGs were related to GO terms associated with responses to different stimuli including response to organic (hormonal) substance, to external stimulus, and to stress. Several DEGs making the most contribution to the inter-strain differences were detected including the Ephx2, which was earlier defined as a major candidate gene in the studies of transcriptional profiles in different tissues/organs (hypothalamus, adrenal gland and kidney) of ISIAH rats.ConclusionsThe results of the study showed that inter-strain differences in ISIAH and WAG brain stem functioning might be a result of the imbalance in processes leading to the pathology development and those, exerting the compensatory effects. The data obtained in this study are useful for a better understanding of the genetic mechanisms underlying the complexity of the brain stem processes in ISIAH rats, which are a model of stress-sensitive form of hypertension.
Highlights
Essential hypertension is a widely spread disease with underlying genetic predispositions, many of which still remain unknown
For better understanding of the molecular basis underlying the brain mechanisms initiating essential hypertension, a number of animal models are widely used [10, 11]. These studies underscore the complexity of genetic mechanisms involved in the blood pressure (BP) regulation and point out that phenotypic appearance may depend on the differences in genetic background and/or physiological conditions
The aim of the current work was to perform the comparative analysis of brain stem transcriptomes in hypertensive Inherited Stress Induced Arterial Hypertension (ISIAH) and normotensive WAG (Wistar Albino Glaxo) rats and to reveal the differentially expressed genes (DEGs), which may play the key role in brain stem functioning, and metabolic pathways contributing to the stress-sensitive hypertension
Summary
Essential (primary) hypertension is a widely spread disease with underlying genetic predispositions, many of which still remain unknown. The brain stem neurons control the sympathetic nerve activity [5] and play important role in regulation of arterial pressure [6,7,8,9]. For better understanding of the molecular basis underlying the brain mechanisms initiating essential hypertension, a number of animal models are widely used [10, 11]. These studies underscore the complexity of genetic mechanisms involved in the blood pressure (BP) regulation and point out that phenotypic appearance may depend on the differences in genetic background and/or physiological conditions. The brain stem neurons are essential for the homeostatic regulation of arterial pressure as they control baroreflex and sympathetic nerve activity. RNA-Seq analysis of the brain stems from the hypertensive ISIAH and normotensive control WAG (Wistar Albino Glaxo) rats was performed to identify the differentially expressed genes (DEGs) and the main central mechanisms (biological processes and metabolic pathways) contributing to the hypertensive state in the ISIAH rats
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