title: Controlled hypertension induces cerebrovascular and gene alterations in Cyp1a1-Ren2 transgenic rats.
abstract: 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.
authors.affiliation: Centre for Neuroregeneration, University of Edinburgh, Edinburgh, UK.
authors.forename: Mercede A
authors.initials: MA
authors.lastname: Pannozzo
authors.affiliation: Centre for Neuroregeneration, University of Edinburgh, Edinburgh, UK; Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Holland
authors.affiliation: Centre for Neuroregeneration, University of Edinburgh, Edinburgh, UK.
authors.forename: Gillian
authors.initials: G
authors.lastname: Scullion
authors.affiliation: Arkgenomics, Roslin Institute & R(D)SVS, University of Edinburgh, Edinburgh, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Talbot
authors.affiliation: BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
authors.forename: John J
authors.initials: JJ
authors.lastname: Mullins
authors.affiliation: Centre for Neuroregeneration, University of Edinburgh, Edinburgh, UK; Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, UK. Electronic address: karen.horsburgh@ed.ac.uk.
authors.forename: Karen
authors.initials: K
authors.lastname: Horsburgh
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000235:genetics; D001812:Blood-Brain Barrier / Q000502:physiology; D002561:Cerebrovascular Disorders / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology; D006973:Hypertension / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D017628:Microglia / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D055647:Rats, Transgenic; D012083:Renin / Q000235:genetics*; D059467:Transcriptome
chemical_list: C535029:Ren2 protein, rat; D019363:Cytochrome P-450 CYP1A1; D012083:Renin
keywords: Hypertension; animal models; cerebrovasculature