Abstract
BackgroundNumerous studies have shown sex differences in the onset and severity of hypertension. Despite these sex-differences the majority of animal studies are carried out in males. This study investigated expression changes in both male and female hypertensive mouse kidneys to identify common mechanisms that may be involved in the development of hypertension.MethodsThe Schlager hypertensive mouse model (BPH/2J) and its normotensive control (BPN/3J) were used in this study. Radiotelemetry was performed on 12 to 13 week old BPH/2J and BPN/3J male and female animals. Affymetrix GeneChip Mouse Gene 1.0 ST Arrays were performed in kidney tissue from 12 week old BPH/2J and BPN/3J male and female mice (n = 6/group). Genes that were differentially expressed in both male and female datasets were validated using qPCR.ResultsSystolic arterial pressure and heart rate was significantly higher in BPH/2J mice compared with BPN/3J mice in both males and females. Microarray analysis identified 153 differentially expressed genes that were common between males and females (70 upregulated and 83 downregulated). We validated 15 genes by qPCR. Genes involved in sympathetic activity (Hdc, Cndp2), vascular ageing (Edn3), and telomere maintenance (Mcm6) were identified as being differentially expressed between BPH/2J and BPN/3J comparisons. Many of these genes also exhibited expression differences between males and females within a strain.ConclusionsThis study utilised data from both male and female animals to identify a number of genes that may be involved in the development of hypertension. We show that female data can be used to refine candidate genes and pathways, as well as highlight potential mechanisms to explain the differences in prevalence and severity of disease between men and women.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-014-0101-x) contains supplementary material, which is available to authorized users.
Highlights
Numerous studies have shown sex differences in the onset and severity of hypertension
Previous radiotelemetry studies on 18 to 20 week old males have shown that blood pressure of BPH/2J hypertensive mice is consistently high and BPN/3J mice is consistently normal [4]
The data obtained has been deposited in the NCBI Gene Expression Omnibus (GEO) database according to the MIAME guidelines
Summary
Numerous studies have shown sex differences in the onset and severity of hypertension. Despite these sex-differences the majority of animal studies are carried out in males. This study investigated expression changes in both male and female hypertensive mouse kidneys to identify common mechanisms that may be involved in the development of hypertension. Significant sex differences in incidence and severity have long been recognized in the prevalence of hypertension [1]. These differences between males and females have suggested that the pathogenesis of human hypertension is modified by sex. The underlying mechanism that leads to disease may be common to both sexes. The majority of studies utilising animal models of disease are carried out in
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