Analysis of genes causing hypertension and stroke in spontaneously hypertensive rats: Gene expression profiles in the brain

Hypertension is associated with gut bacterial dysbiosis and gut pathology in animal models and people. Butyrate-producing gut bacteria are decreased in hypertension. RNA-seq analysis of gut colonic organoids prepared from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats was used to test the hypothesis that impaired interactions between the gut microbiome and gut epithelium are involved and that these would be remediated with butyrate supplementation. Gene expressions in immune responses including antigen presentation and antiviral pathways were decreased in the gut epithelium of the SHR in organoids and confirmed in vivo; these deficits were corrected by butyrate supplementation. Deficits in gene expression driving epithelial proliferation and differentiation were also observed in SHR. These findings highlight the importance of aligned interactions of the gut microbiome and gut immune responses to blood pressure homeostasis.

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Differential renal gene expression in prehypertensive and hypertensive spontaneously hypertensive rats

AJP Renal Physiology ◽

10.1152/ajprenal.00354.2004 ◽

2005 ◽

Vol 289 (3) ◽

pp. F552-F561 ◽

Cited By ~ 23

Author(s):

J. M. Seubert ◽

F. Xu ◽

J. P. Graves ◽

J. B. Collins ◽

S. O. Sieber ◽

...

Keyword(s):

Gene Expression ◽

Spontaneously Hypertensive Rats ◽

Expression Profiles ◽

Expression Patterns ◽

Differentially Expressed ◽

Gene Expression Patterns ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Time Points ◽

Age Related

Development of hypertension stems from both environmental and genetic factors wherein the kidney plays a central role. Spontaneously hypertensive rats (SHR) and the nonhypertensive Wistar-Kyoto (WKY) controls are widely used as a model for studying hypertension. The present study examined the renal gene expression profiles between SHR and WKY at a prehypertensive stage (3 wk of age) and hypertensive stage (9 wk of age). Additionally, age-related changes in gene expression patterns were examined from 3 to 9 wk in both WKY and SHR. Five to six individual kidney samples of the same experimental group were pooled together, and quadruplicate hybridizations were performed using the National Institute of Environmental Health Sciences Rat version 2.0 Chip, which contains ∼6,700 genes. Twenty two genes were found to be differentially expressed between SHR and WKY at 3 wk of age, and 104 genes were differentially expressed at 9 wk of age. Soluble epoxide hydrolase ( Ephx2) was found to be significantly upregulated in SHR at both time points and was the predominant outlier. Conversely, elastase 1 ( Ela1) was found to be the predominant gene downregulated in SHR at both time points. Analysis of profiles at 3 vs. 9 wk of age identified 508 differentially expressed genes in WKY rats. In contrast, only 211 genes were found to be differentially expressed during this time period in SHR. The altered gene expression patterns observed in the age-related analysis suggested significant differences in the vascular extracellular matrix system between SHR and WKY kidney. Together, our data highlight the complexity of hypertension and the numerous genes involved in and affected by this condition.

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Trpv4 involvement in the sex differences in blood pressure regulation in spontaneously hypertensive rats

Physiological Genomics ◽

10.1152/physiolgenomics.00096.2017 ◽

2018 ◽

Vol 50 (4) ◽

pp. 272-286 ◽

Cited By ~ 1

Author(s):

Makiko Onishi ◽

Ko Yamanaka ◽

Yasunori Miyamoto ◽

Hidefumi Waki ◽

Sabine Gouraud

Keyword(s):

Gene Expression ◽

Blood Pressure ◽

Sex Differences ◽

Spontaneously Hypertensive Rats ◽

Expression Profiles ◽

Premenopausal Women ◽

Blood Pressure Regulation ◽

Pressure Regulation ◽

Hypertensive Rats ◽

Spontaneously Hypertensive

Arterial pressure (AP) is lower in premenopausal women than in men of a similar age. Premenopausal women exhibit a lower sympathetic activity and a greater baroreceptor reflex; however, mechanisms controlling sex differences in blood pressure regulation are not well understood. We hypothesized that different neuronal functions in the cardiovascular centers of the brains of men and women may contribute to the sex difference in cardiovascular homeostasis. Our previous studies on male spontaneously hypertensive rats (SHRs) and their normotensive counterparts, Wistar Kyoto (WKY) rats, revealed that the gene-expression profile of the nucleus tractus solitarius (NTS), a region of the medulla oblongata that is pivotal for regulating the set point of AP, is strongly associated with AP. Thus, we hypothesized that gene-expression profiles in the rat NTS are related to sex differences in AP regulation. Because female SHRs clearly exhibit lower AP than their male counterparts of a similar age, we investigated whether SHR NTS exhibits sex differences in gene expression by using microarray and RT-qPCR experiments. The transcript for transient receptor potential cation channel subfamily V member 4 ( Trpv4) was found to be upregulated in SHR NTS in females compared with that in males. The channel was expressed in neurons and glial cells within NTS. The TRPV4 agonist 4-alpha-phorbol-12,13-didecanoate (4α-PDD) decreased blood pressure when injected into NTS of rats. These findings suggest that altered TRPV4 expression might be involved in the sex differences in blood pressure regulation.

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Transcriptome of the NTS in exercise-trained spontaneously hypertensive rats: implications for NTS function and plasticity in regulating blood pressure

Physiological Genomics ◽

10.1152/physiolgenomics.00074.2012 ◽

2013 ◽

Vol 45 (1) ◽

pp. 58-67 ◽

Cited By ~ 10

Author(s):

Hidefumi Waki ◽

Sabine S. Gouraud ◽

Mohammad E. R. Bhuiyan ◽

Miwa Takagishi ◽

Toshiya Yamazaki ◽

...

Keyword(s):

Gene Expression ◽

Blood Pressure ◽

Spontaneously Hypertensive Rats ◽

Expression Profiles ◽

Potential Contribution ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Daily Exercise ◽

Receptor Interactions

The nucleus tractus solitarii (NTS) controls the cardiovascular system during exercise, and alteration of its function may underlie exercise-induced cardiovascular adaptation. To understand the molecular basis of the NTS's plasticity in regulating blood pressure (BP) and its potential contribution to the antihypertensive effects, we characterized the gene expression profiles at the level of the NTS after long-term daily wheel running in spontaneously hypertensive rats (SHRs). Genome-wide microarray analysis was performed to screen for differentially expressed genes in the NTS between exercise-trained (12 wk) and control SHRs. Pathway analysis using the Kyoto Encyclopedia of Genes and Genomes database revealed that daily exercise altered the expression levels of NTS genes that are functionally associated with metabolic pathways (5 genes), neuroactive ligand-receptor interactions (4 genes), cell adhesion molecules (3 genes), and cytokine-cytokine receptor interactions (3 genes). One of the genes that belonged to the neuroactive ligand-receptor interactions category was histamine receptor H1. Since we confirmed that the pressor response induced by activation of this receptor is increased after long-term daily exercise, it is suggested that functional plasticity in the histaminergic system may mediate the facilitation of blood pressure control in response to exercise but may not be involved in the lowered basal BP level found in exercise-trained SHRs. Since abnormal inflammatory states in the NTS are known to be prohypertensive in SHRs, altered gene expression of the inflammatory molecules identified in this study may be related to the antihypertensive effects in exercise-trained SHRs, although such speculation awaits functional validation.

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