The renal function plays a leading role in long-term control of arterial blood pressure (BP). The goal of the study was to identify the differentially expressed genes (DEGs) related to hypertension and the pathways contributing to the differences in renal functioning in hypertensive ISIAH and normotensive WAG rats.Design and Method:
The RNA-Seq approach was used for comparative transcriptional profiling of renal cortex in 3-month old male rats with inherited stress-induced arterial hypertension (ISIAH/Icgn) and normotensive Wistar Albino Glaxo (WAG/GSto-Icgn) rats. The differential expression of several genes was validated by real-time PCR.Results:
The 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 BP. Six of these genes are known as genes related to renal hypertension. Sixty of the detected DEGs are referred to in Rat Genome Database as associated with renal diseases, including renal fibrosis, renal insufficiency, glomerulonephritis, diabetic nephropathy, and nephrosclerosis. The functional annotation of DEGs suggested the existence of the hormone dependent interstrain differences in renal cortex function. Multiple DEGs were associated with blood circulation, and with the response to stress (including oxidative stress, hypoxia, fluid shear stress), its regulation and several other processes (Figure). Metabolic pathways significantly enriched with DEGs were related to immune system function, to steroid hormone biosynthesis, tryptophan, glutathione, nitrogen, and drug metabolism. Two DEGs associated with hypertension (Ephx2, Glp1r) and showing the highest differences in expression in ISIAH and WAG renal cortex were considered as candidates for further studies.Conclusions:
The 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 functioning and hypertension development.