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• W2152565418 abstract "The exact mechanism underlying regional cerebral hypoperfusion in the early phase of Alzheimer's disease (AD) is not understood. We have shown in isolated porcine cerebral arteries that stimulation of sympathetic α7-nicotinic acetylcholine receptors (α7-nAChRs) causes release of nitric oxide in parasympathetic nitrergic nerves and vasodilation. We therefore examined if β-amyloid peptides (Aβs), which play a key role in pathogenesis of AD, blocked sympathetic α7-nAChRs leading to reduced neurogenic nitrergic dilation in isolated porcine basilar arteries, using in vitro tissue bath, calcium image, and patch clamping techniques. The results indicated that Aβ 1–40 , but not Aβ 40–1 , blocked relaxation of endothelium-denuded basilar arterial rings induced by nicotine (100μ;mol/L) and choline (1 mmol/L) without affecting that induced by sodium nitroprusside or isoproterenol. In cultured superior cervical ganglion (SCG) cells, Aβ 1–40 , but not Aβ 40–1 , blocked choline- and nicotine-induced calcium influx and inward currents. The Aβ blockade of the nitrergic vasodilation and inward currents, but not that of calcium influx, was prevented by acute pretreatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors mevastatin and lovastatin. These results suggest that Aβ 1–40 blocks cerebral perivascular sympathetic α7-nAChRs, resulting in the attenuation of cerebral nitrergic neurogenic vasodilation. This effect of Aβ may be responsible in part for cerebral hypoperfusion occurred in the early phase of the AD, which may be prevented by statins most likely because of their effects independent of cholesterol lowering. Statins may offer an alternative strategy in the prevention and treatment of AD." @default.
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• W2152565418 date "2005-09-28" @default.
• W2152565418 modified "2023-10-16" @default.
• W2152565418 title "Statins Prevent β-Amyloid Inhibition of Sympathetic α7-nAChR-Mediated Nitrergic Neurogenic Dilation in Porcine Basilar Arteries" @default.
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• W2152565418 doi "https://doi.org/10.1038/sj.jcbfm.9600232" @default.
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