Whole rat DNA array survey for candidate genes related to hypertension in kidneys from three spontaneously hypertensive rat substrains at two stages of age and with hypotensive induction caused by hydralazine hydrochloride

Abstract

Abstract. Clarification of the genetic nature and more effective care for hypertension are required, given the high incidences of cardiovascular and cerebrovascular mortality. Thus, we surveyed candidate genes for hypertension with rat whole gene DNA microarrays using three novel methods. Gene expression analyses were conducted as follows: Method 1, three types of spontaneously hypertensive rat (SHR) substrains, SHR, strokeprone SHR (SHRSP) and malignant type of SHRSP (M-SHRSP) were used and compared to normotensive Wistar Kyoto rats; Method 2, the expressed genes between rats of different ages were compared for different blood pressures; and Method 3, genes that were expressed in rats treated with or without an acute hypotensive stimulus, the antihypertensive hydralazine hydrochloride, were compared. This approach identified dozens of genes, including Dusp15, Cyp8b1, Armc 3, Gtpbp4, Mettl2, Mapk14, Prkar2b, frame 12, Anxa13, Ephx2, Myr8 and Pcdh9 by Method 1; Cyp2C and Atp12a by Method 2; and Kcnc3, Vnn1, TC560558 and Gabrq and a number of unknown genes by Methods 2 and 3, as probable candidate genes for hypertension in SHR substrains. Ephx2 was previously reported as a candidate gene in SHRs; however other genes were identified for the first time in this study. Since it was not always possible to completely demonstrate that these genes are responsible for hypertension in SHRs, further research into true candidate genes that participate in the genesis of hypertension in SHR substrains is warranted.

A custom rat and baboon hypertension gene array to compare experimental models

“…Interestingly, many of the systems that are commonly thought to play major roles in high blood pressure, nitric oxide synthase, superoxide, renin-angiotensin-aldosterone system showed very little if any changes between the sham and DOCA-salt treatment. No genes detected in this array were similar to those found by Kinoshita et al(43) when they performed a whole rat DNA array survey for candidate genes in kidneys from three spontaneously hypertensive rat substrains at two stages of age, including an analysis of kidneys from animals treated with the antihypertensive agent hydralizine hydrochloride. While this is a genetic based model of hypertension, it punctuates the need for further studies.…”

Differential gene expression in multiple neurological, inflammatory and connective tissue pathways in a spontaneous model of human small vessel stroke

“…The genetic factors that render the SHRSP stroke‐prone are also poorly understood. Known differences between SHRSP and WKY include STR‐2 quantitative trait loci on chromosome 5 colocalized with genes encoding atrial and brain natriuretic peptides [19–21], a single‐nucleotide polymorphism (SNP) on chromosome 2 (R202H) associated with reduced glutathione S‐transferase expression [22], and, from a recent GWAS, a number of candidate genes for hypertension in spontaneously hypertensive rat substrains [23], but which are not known to affect stroke directly [24].…”

Single-Nucleotide Polymorphisms (SNPs) Both Associated with Hypertension and Contributing to Accelerated-Senescence Traits in OXYS Rats

“…In our work, the RGD was employed to identify the genes associated with hypertension. On the other hand, according to the results presented in Reference [14], Gtpbp4 (GTP-binding protein 4) is a candidate gene associated with hypertension in three SHR rat substrains. On the basis of this information, it can be assumed that a nonsynonymous substitution presumably affecting the structure and/or function of GTPBP4 may be associated with hypertension in both OXYS and ISIAH rats.…”