Journal
CURRENT ALZHEIMER RESEARCH
Volume 12, Issue 10, Pages 914-922Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1567205012666151027130135
Keywords
Alzheimer Disease; Angiotensin II; Angiotensin II Receptor Blockers; Cerebrovascular Circulation; Diuretics; Hypertension
Categories
Funding
- Internationale Stichting Alzheimer Onderzoek (ISAO) [11528]
- EU 7th framework LipidiDiet project (FP7) [211696]
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Aims: Hypertension, a risk factor for Alzheimer's disease (AD), is a treatable condition, which offers possibilities for prevention of AD. Elevated angiotensin II (AngII) is an important cause of essential hypertension. AngII has deleterious effects on endothelial function and cerebral blood flow (CBF), which may contribute to AD. AngII blocking agents can thus provide potential candidates to reduce AD risk factors in hypertensive patients. Methods: We studied the effect of 2 months induced hypertension (AngII-infusion via osmotic micropumps) on systolic blood pressure (SBP) and CBF in 10 months-old wild-type (WT) C57bl/6j and A beta PPswe/PS1 Delta E9 (A beta PP/PS1) mice, and treatment with two different antihypertensives, 1) eprosartan mesylate (EM, 0.35mg/kg) or 2) hydrochlorotiazide (HCT, 7.5mg/kg), after 1 month of induced-hypertension. SBP was monitored twice each month via tail cuff plethysmography. CBF was measured with MR by flow-sensitive alternating inversion recovery. Results: Chronic AngII-infusion induced an increase in SBP in both A beta PP/PS1 and WT mice accompanied by a decrease in hippocampal and thalamic CBF only in the A beta PP/PS1 mice. An additional difference between the A beta PP/PS1 mice and WT mice was that SBP was much higher in A beta PP/PS1 mice in both hypertensive and normotensive conditions. Moreover, both antihypertensives were less effective in reducing AngII-induced hypertension to normal levels in A beta PP/PS1 mice, while being effective in WT mice. Conclusions: It can be concluded that AngII-induced elevated SBP results in impaired CBF and a decreased response to blood pressure lowering treatment in a transgenic model of AD. Our findings suggest a relation between midlife hypertension and decreased CBF in an AD mouse model, similar to the relation which has been found in AD patients. This translational mouse model could be used to investigate possible prevention and treatment strategies for AD.
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