P454Vascular abnormalities in spontaneously hypertensive rats: a matter of substrains

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Introduction: 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.

Methods and results: We studied WKY and SHR from three different sources, at 6 weeks and 5 months of age. Both WKY and SHR showed significant differences in blood pressure, body weight, vascular remodeling, endothelial function, and vessel ultrastructure among sublines. Common features in vessels from SHR were an increase in wall thickness, wall-to-lumen ratio, and internal elastic lamina thickness. Using microarrays, we studied miRNA and mRNA expression in resistance arteries from all sublines. Principal component analysis and hierarchical clustering indicated that SHR, but particularly WKY, show clear differences in gene expression among sublines. Overall, 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 miR-132-3p, and type III deiodinase. Comparison of WKY to SHR also yielded differences in gene expression common to all three sublines, including thrombospondin 4.

Conclusions: These results indicate that abnormalities that are associated with hypertension, such as endothelial dysfunction, vascular stiffening, and inward remodeling of small arteries are subline-dependent. Herein both the specific SHR and WKY subline determine the outcome of the comparison. These findings may help to explain apparently discrepant data in literature regarding the pathophysiology of hypertension.

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