Nilvadipine antagonizes both Aβ vasoactivity in isolated arteries, and the reduced cerebral blood flow in APPsw transgenic mice

被引：70

作者：

Paris, D ^{[1
]}

Quadros, A ^{[1
]}

Humphrey, J ^{[1
]}

Patel, N ^{[1
]}

Crescentini, R ^{[1
]}

Crawford, F ^{[1
]}

Mullan, M ^{[1
]}

机构：

[1] Roskamp Inst, Sarasota, FL 34243 USA

来源：

BRAIN RESEARCH | 2004年 / 999卷 / 01期

关键词：

nilvadipine; Alzheimer; abeta; amyloid; cerebral blood flow; transgenic;

D O I：

10.1016/j.brainres.2003.11.061

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The development of Alzheimer's disease (AD) is generally thought to correlate with cerebral accumulation of A. It has previously been shown that A peptides enhance vasoconstriction in isolated arteries and oppose certain vasorelaxants. Moreover, exogenous application of Abeta peptides causes cerebral vasoconstriction in rodents and in transgenic mouse models of AD that overexpress Abeta there is reduced cerebral blood flow. In the present study, we investigated the effect of nilvadipine, a dihydropyridine-type calcium channel blocker, on A induced vasoconstriction in isolated arteries and in vivo on cerebral blood flow (CBF) of an AD transgenic mouse model overexpressing Abeta (Tg APPsw line 2576). Nilvadipine completely inhibited the vasoactivity elicited by Abeta in rat aortae and in human middle cerebral arteries. The effect of a short treatment duration (2 weeks) with nilvadipine on regional CBF was investigated in 13-month-old Tg APPsw mice and control littermates using a laser Doppler imager. Additionally, CBF was also measured in 20-month-old Tg APPsw mice and control littermates that were chronically treated with nilvadipine for 7 months. Untreated Tg APPsw mice showed a reduction of regional CBF compared to their untreated control littermates. Nilvadipine restored cortical perfusion levels in Tg APPsw to values similar to those observed in control littermates without notably affecting the CBF of control mice. All together, these data suggest that nilvadipine might be useful for the treatment of oligemia associated with AD. (C) 2003 Elsevier B.V. All rights reserved.

引用

页码：53 / 61

页数：9

共 39 条

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