Heterogeneity in arterial remodeling among sublines of spontaneously hypertensive rats.
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ABSTRACT: Objectives
Spontaneously hypertensive rats (SHR) have been used frequently as a model for human essential hypertension. However, both the SHR and its normotensive control, the Wistar Kyoto rat (WKY), consist of genetically different sublines. We tested the hypothesis that the pathophysiology of vascular remodeling in hypertension differs among rat sublines.Methods and results
We studied mesenteric resistance arteries of WKY and SHR from three different sources, at 6 weeks and 5 months of age. Sublines of WKY and SHR showed differences in blood pressure, body weight, vascular remodeling, endothelial function, and vessel ultrastructure. Common features in small mesenteric arteries from SHR were an increase in wall thickness, wall-to-lumen ratio, and internal elastic lamina thickness.Conclusions
Endothelial dysfunction, vascular stiffening, and inward remodeling of small mesenteric arteries are not common features of hypertension, but are subline-dependent. Differences in genetic background associate with different types of vascular remodeling in hypertensive rats.
SUBMITTER: Bakker EN
PROVIDER: S-EPMC4175999 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Spontaneously hypertensive rats (SHR) have been used frequently as a model for human essential hypertension. However, both the SHR and its normotensive control, the Wistar Kyoto rat (WKY), consist of genetically different sublines. We tested the hypothesis that discrepant data in literature regarding the pathophysiology of vascular remodeling in hypertension result from the use of different rat sublines. Using micro-arrays, we studied miRNA and mRNA expression in resistance arteries of WKY and SHR from three different sources, at 6 weeks and 5 months of age. Both WKY and SHR showed an age-related expression pattern that involved many genes related to the extracellular matrix. In SHR, this pattern was more extensive and included a specific increase in miR132-3p, and type III deiodinase. Direct comparison of WKY to SHR also yielded differences in expression, including thrombospondin 4. Heterogeneity in gene expression among sublines was associated with differences in blood pressure, body weight, vascular remodeling, endothelial function, and vessel ultrastructure. Common features in vessels from SHR were an increase in wall thickness, wall-to-lumen ratio, and internal elastic lamina thickness. These results indicate that endothelial dysfunction, vascular stiffening, and inward remodeling of small arteries are not common features of hypertension, but are subline-dependent. Relatively minor differences in genetic background associate with different types of vascular remodeling in hypertensive rats. The clinical implication of this study is that more research into personalized treatment in hypertension is warranted.
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