高血压损害阿尔茨海默病小鼠模型的脑血流量

Title:Hypertension Impairs Cerebral Blood Flow in a Mouse Model for Alzheimer’s Disease

Volume: 12 Issue: 10

Author(s): Maximilian Wiesmann, Carmen Capone, Valerio Zerbi, Laura Mellendijk, Arend Heerschap, Jurgen A.H.R. Claassen and Amanda J. Kiliaan

Affiliation:

关键词: 阿尔茨海默病、血管紧张素Ⅱ、血管紧张素Ⅱ受体阻断剂、脑血管循环、利尿剂、高血压。

摘要: 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 AβPPswe/PS1ΔE9 (AβPP/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 AβPP/PS1 and WT mice accompanied by a decrease in hippocampal and thalamic CBF only in the AβPP/PS1 mice. An additional difference between the AβPP/PS1 mice and WT mice was that SBP was much higher in AβPP/PS1 mice in both hypertensive and normotensive conditions. Moreover, both antihypertensives were less effective in reducing AngII-induced hypertension to normal levels in AβPP/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.

Cite this article as:

Maximilian Wiesmann, Carmen Capone, Valerio Zerbi, Laura Mellendijk, Arend Heerschap, Jurgen A.H.R. Claassen and Amanda J. Kiliaan , Hypertension Impairs Cerebral Blood Flow in a Mouse Model for Alzheimer’s Disease, Current Alzheimer Research 2015; 12 (10) . https://dx.doi.org/10.2174/1567205012666151027130135