RESUMO
Hypertension is linked with an increased risk of white matter hyperintensities; however, recent findings have questioned this association. We examined whether hypertension and additional cerebrovascular risk factors impacted on white matter integrity in an inducible hypertensive rat. No white matter hyperintensities were observed on magnetic resonance imaging either alone or in conjunction with ageing and high-fat diet. Aged hypertensive rats that were fed a high-fat diet had moderately reduced fractional anisotropy in the corpus callosum with no overt pathological features. Herein we show that moderate hypertension alone or with additional risk factors has minimal impact on white matter integrity in this model.
Assuntos
Envelhecimento , Citocromo P-450 CYP1A1/genética , Hipertensão/metabolismo , Renina , Substância Branca/metabolismo , Envelhecimento/genética , Envelhecimento/metabolismo , Envelhecimento/patologia , Animais , Corpo Caloso/metabolismo , Corpo Caloso/patologia , Gorduras na Dieta/efeitos adversos , Gorduras na Dieta/farmacologia , Hipertensão/patologia , Camundongos , Ratos , Ratos Endogâmicos F344 , Ratos Transgênicos , Renina/biossíntese , Renina/genética , Substância Branca/patologiaRESUMO
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.
