PS 07-02 COMPARATIVE TRANSCRIPTIONAL PROFILING OF HYPOTHALAMUS IN ISIAH RATS WITH INHERITED STRESS-INDUCED ARTERIAL HYPERTENSION AND NORMOTENSIVE WISTAR ALBINO GLAXO RATS

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Abstract

Objective:

Most forms of hypertension are associated with a wide variety of functional changes in the hypothalamus. The studies on different animal models lead to a better understanding of the processes responsible for the increased sympathetic outflow and hypertension development in humans. The goal of the study was to identify the differentially expressed genes (DEGs) and pathways involved in the differences of hypothalamic functions in hypertensive ISIAH and normotensive WAG rats.

Design and Method:

The RNA-Seq approach was used for comparative transcriptional profiling of hypothalamus in 3-month old male rats with inherited stress-induced arterial hypertension (ISIAH/Icgn) and normotensive Wistar Albino Glaxo (WAG/GSto-Icgn) rats.

Results:

The analysis revealed 139 DEGs in the hypothalami of ISIAH and WAG rats. Eighteen of these are known as associated with arterial hypertension. The functional annotation of DEGs revealed the most significantly affected processes contributing to the hypertension development in the ISIAH rats (Figure). The most significantly affected metabolic pathways were those associated with the immune system functioning, cell adhesion molecules and the metabolism of retinol and arachidonic acid. Three of the top 40 DEGs making the greatest contribution to the interstrain differences and known as associated with hypertension (Ephx2, Cst3 and Ltbp2) were considered as suitable targets for further studies of molecular mechanisms of the stress-sensitive hypertension development. Several DEGs were found to be common between hypothalamic transcriptomes of ISIAH rats and Schlager mice with established neurogenic hypertension.

Conclusions:

The results of this study revealed multiple DEGs and possible mechanisms specifying the hypothalamic function in the hypertensive ISIAH rats, reproducing the human stress-sensitive hypertensive state with predominant involvement of the neuroendocrine hypothalamic-pituitary-adrenal and sympathoadrenal axes. These results provide a basis for further investigation of the signalling mechanisms that affect hypothalamic output related to stress-sensitive hypertension development.

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