The functions of the hypothalamic adrenal cortical and sympathetic adrenal medullary systems were studied in rats with inherited stress-induced arterial hypertension (ISIAH strain). A characteristic feature of the ISIAH strain is an increase in arterial blood pressure measured both under basal conditions and after restraint stress in particular. In the control ISIAH rats, the basal plasma ACTH concentration was slightly lower than that in the normotensive Wistar albino Glaxo (WAG) rats, and no differences were found in plasma corticosterone. However, the 0 . 5-h restraint stress produced higher activation of the adrenal cortex in the ISIAH rats. Gluco-and mineralocorticoid responses to the blood volume reduction stresses and ACTH and corticosterone responses to social stress were stronger in the ISIAH than in the control WAG rats. An increase in epinephrine content in adrenals in the basal state and enhanced response of the sympathetic adrenal medullary system to handling stress were observed in the ISIAH rats. Restraint stress produced significantly higher expression of genes encoding corticotropinreleasing hormone-mRNA in hypothalamus and proopiomelanocortin-mRNA in pituitary in the ISIAH than in the WAG rats. Restraint stress produced a decrease in glucocorticoid receptor (GR) gene expression (GR-mRNA) in hippocampus in the ISIAH, but not in the WAG rats. A persistent increase in tyrosine hydroxylase-mRNA in adrenals of the ISIAH rats was found. It is concluded that the ISIAH rat strain is an appropriate model of stress-sensitive hypertension with the predominant involvement of the hypothalamic adrenal cortical and sympathetic adrenal medullary systems in its pathogenesis.

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BackgroundThe adrenals are known as an important link in pathogenesis of arterial hypertensive disease. The study was directed to the adrenal transcriptome analysis in ISIAH rats with stress-sensitive arterial hypertension and predominant involvement in pathogenesis of the hypothalamic-pituitary-adrenal and sympathoadrenal systems.ResultsThe RNA-Seq approach was used to perform the comparative adrenal transcriptome profiling in hypertensive ISIAH and normotensive WAG rats. Multiple differentially expressed genes (DEGs) related to different biological processes and metabolic pathways were detected.The discussion of the results helped to prioritize the several DEGs as the promising candidates for further studies of the genetic background underlying the stress-sensitive hypertension development in the ISIAH rats. Two of these were transcription factor genes (Nr4a3 and Ppard), which may be related to the predominant activation of the sympathetic-adrenal medullary axis in ISIAH rats. The other genes are known as associated with hypertension and were defined in the current study as DEGs making the most significant contribution to the inter-strain differences. Four of them (Avpr1a, Hsd11b2, Agt, Ephx2) may provoke the hypertension development, and Mpo may contribute to insulin resistance and inflammation in the ISIAH rats.ConclusionsThe study strongly highlighted the complex nature of the pathogenesis of stress-sensitive hypertension. The data obtained may be useful for identifying the common molecular determinants in different animal models of arterial hypertension, which may be potentially used as therapeutic targets for pharmacological intervention.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3354-2) contains supplementary material, which is available to authorized users.

BackgroundThe renal function plays a leading role in long-term control of arterial pressure. The comparative analysis of renal cortex transcriptome in ISIAH rats with inherited stress-induced arterial hypertension and normotensive WAG rats was performed using RNA-Seq approach. The goal of the study was to identify the differentially expressed genes (DEGs) related to hypertension and to detect the pathways contributing to the differences in renal functions in ISIAH and WAG rats.ResultsThe analysis revealed 716 genes differentially expressed in renal cortex of ISIAH and WAG rats, 42 of them were associated with arterial hypertension and regulation of blood pressure (BP). Several Gene Ontology (GO) terms significantly enriched with DEGs suggested the existence of the hormone dependent interstrain differences in renal cortex function. Multiple DEGs were associated with regulation of blood pressure and blood circulation, with the response to stress (including oxidative stress, hypoxia, and fluid shear stress) and its regulation. Several other processes which may contribute to hypertension development in ISIAH rats were: ion transport, regulation of calcium ion transport, homeostatic process, tissue remodeling, immune system process and regulation of immune response.KEGG analysis marked out several pathways significantly enriched with DEGs related to immune system function, to steroid hormone biosynthesis, tryptophan, glutathione, nitrogen, and drug metabolism.ConclusionsThe results of the study provide a basis for identification of potential biomarkers of stress-sensitive hypertension and for further investigation of the mechanisms that affect renal cortex function and hypertension development.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-015-0306-9) contains supplementary material, which is available to authorized users.

BackgroundThe changes in the renal function leading to a reduction of medullary blood flow can have a great impact on sodium and water homeostasis and on the long-term control of arterial blood pressure. The RNA-Seq approach was used for transcriptome profiling of the renal medulla from hypertensive ISIAH and normotensive WAG rats to uncover the genetic basis of the changes underlying the renal medulla function in the ISIAH rats being a model of the stress-sensitive arterial hypertension and to reveal the genes which possibly may contribute to the alterations in medullary blood flow.ResultsMultiple DEGs specifying the function of renal medulla in ISIAH rats were revealed. The group of DEGs described by Gene Ontology term ‘oxidation reduction’ was the most significantly enriched one. The other groups of DEGs related to response to external stimulus, response to hormone (endogenous) stimulus, response to stress, and homeostatic process provide the molecular basis for integrated responses to homeostasis disturbances in the renal medulla of the ISIAH rats. Several DEGs, which may modulate the renal medulla blood flow, were detected. The reduced transcription of Nos3 pointed to the possible reduction of the blood flow in the renal medulla of ISIAH rats.ConclusionsThe generated data may be useful for comparison with those from different models of hypertension and for identifying the common molecular determinants contributing to disease manifestation, which may be potentially used as new pharmacological targets.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-016-0462-6) contains supplementary material, which is available to authorized users.