Abstract
BackgroundThe hypothalamus has an important role in the onset and maintenance of hypertension and stress responses. Rats with inherited stress-induced arterial hypertension (ISIAH), reproducing the human stress-sensitive hypertensive state with predominant involvement of the neuroendocrine hypothalamic-pituitary-adrenal and sympathoadrenal axes, were used for analysis of the hypothalamus transcriptome.ResultsRNA-seq analysis revealed 139 genes differentially expressed in the hypothalami of hypertensive ISIAH and normotensive Wistar Albino Glaxo (WAG) rats. According to the annotation in databases, 18 of the differentially expressed genes (DEGs) were associated with arterial hypertension. The Gene Ontology (GO) functional annotation showed that these genes were related to different biological processes that may contribute to the hypertension development in the ISIAH rats. The most significantly affected processes were the following: regulation of hormone levels, immune system process, regulation of response to stimulus, blood circulation, response to stress, response to hormone stimulus, transport, metabolic processes, and endocrine system development. The most significantly affected metabolic pathways were those associated with the function of the immune system and cell adhesion molecules and the metabolism of retinol and arachidonic acid. Of the top 40 DEGs making the greatest contribution to the interstrain differences, there were 3 genes (Ephx2, Cst3 and Ltbp2) associated with hypertension that were considered to be suitable for further studies as potential targets for the stress-sensitive hypertension therapy. Seven DEGs were found to be common between hypothalamic transcriptomes of ISIAH rats and Schlager mice with established neurogenic hypertension.ConclusionsThe results of this study revealed multiple DEGs and possible mechanisms specifying the hypothalamic function in the hypertensive ISIAH rats. These results provide a basis for further investigation of the signalling mechanisms that affect hypothalamic output related to stress-sensitive hypertension development.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-015-0307-8) contains supplementary material, which is available to authorized users.
Highlights
The hypothalamus has an important role in the onset and maintenance of hypertension and stress responses
Altogether, 11,369 annotated genes were defined as being expressed in the hypothalami of inherited stress-induced arterial hypertension (ISIAH) and Wistar Albino Glaxo (WAG) rats and were used in comparative expression analysis, which revealed 139 differentially expressed genes (DEG)
Functional annotation of DEGs The most significant Gene Ontology (GO) terms for biological processes, which may be related to the hypertensive state of ISIAH rats, and genes in related groups of DEGs are represented in Additional file 2
Summary
The hypothalamus has an important role in the onset and maintenance of hypertension and stress responses. Rats with inherited stress-induced arterial hypertension (ISIAH), reproducing the human stress-sensitive hypertensive state with predominant involvement of the neuroendocrine hypothalamic-pituitary-adrenal and sympathoadrenal axes, were used for analysis of the hypothalamus transcriptome. As the studies on experimental animal models provide valuable information to elucidate the nature of polygenic traits [5], a number of animal models for essential hypertension are widely used. One of these is the ISIAH (Inherited Stress-Induced Arterial Hypertension) rat strain, which has been developed to study the mechanisms of stress-sensitive hypertension and its complications. Earlier studies showed that the ISIAH rats may be regarded as a model for the human stress sensitive hypertensive disease with predominant involvement of the neuroendocrine hypothalamic-pituitaryadrenal (HPA) and sympathoadrenal systems in the pathogenesis of the hypertensive state [9]
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