Journal
JOURNAL OF THE AMERICAN SOCIETY OF HYPERTENSION
Volume 7, Issue 6, Pages 411-419Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jash.2013.07.011
Keywords
Hypertension; cerebrovasculature; animal models
Categories
Funding
- Age UK
- Alzheimer's Research UK
- Alzheimer Society
- BBSRC
- EPSRC
- ESRC
- MRC
- University of Edinburgh, School of Biomedical Sciences
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Hypertension is a major risk factor for small vessel disease and dementia, but the pathogenic mechanisms are not fully known. This study aimed to assess cerebrovascular alterations in response to different durations (4 or 6 months) of controlled hypertension in an inducible transgenic rat model of hypertension (Cyp1a1-Ren2) as compared with normotensive litter mate controls. After 6 months of hypertension as compared with controls, a significant reduction in vascular width was paralleled by an increase in the protein levels of claudin-5, an endothelial tight junction protein. Notably, vascular alterations were associated with increased microglia, and these changes were preceded by increased eNOS expression. Investigation of global gene expression by microarray analysis indicated alterations in predominantly growth factor related genes. Herein, we show that modest, sustained levels of hypertension are sufficient to cause cerebrovascular alterations accompanied by endothelial and inflammatory changes. These changes are paralleled by alterations in growth factor expression suggestive of a mechanistic role. (C) 2013 American Society of Hypertension. All rights reserved.
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