Brain Res. 2004 Feb 27;999(1):53-61.
Nilvadipine antagonizes both Abeta vasoactivity in isolated arteries,
and the reduced cerebral blood flow in APPsw transgenic
mice.
Paris D, Quadros A, Humphrey J, Patel N, Crescentini R,
Crawford F, Mullan M.
The Roskamp Institute,
The development of Alzheimer's disease (AD) is generally thought to correlate
with cerebral accumulation of Abeta. It has
previously been shown that Abeta 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 Abeta 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.
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Keywords: Nilvadipine, Abeta, Antagonizes, reduced, cerebral, blood, APPsw, transgenic mice, Brain Res.