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Microvessels underwent initial vasoconstriction (2 \u00b5M noradrenaline) then treatment with either 0.5 mM glutamate or 100 \u00b5M NMDA. In acute brain slices from young mice (&lt;20 weeks) the glutamate and NMDA treatment led to dilation of capillaries in cortex and hippocampus, but not in aged CVN mice (&gt;30 weeks, with AD pathology). Furthermore, 1 mM adenosine restored pre-constricted capillaries to control levels in WT but not in aged CVN brain slices. Stimulation of endothelial ET-1 receptors (10 nM ET-1) showed enhanced vasoconstriction in hippocampal capillaries of aged CVN slices, but blockade of both ET-1A\/1B receptors did not alter basal capillary tone in aged CVN slices. Stimulation-evoked hippocampal CBF in vivo was significantly reduced in aged CVN mice. These results provide evidence for a progressive, complex age- and AD pathology-related impairment of vascular reactivity and vasodilation in the CVN model. 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