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A beta-peptides enhance vasoconstriction in cerebral circulation.
1Center for Clinical and Molecular Neurobiology, Department of Neurology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
American Journal of Physiology. Heart and Circulatory Physiology
|November 16, 2001
Summary
Amyloid-beta peptides constrict cerebral blood vessels and worsen vasoconstriction, potentially contributing to Alzheimer's dementia. These effects are linked to free radical production and can be reversed by antioxidants.
Area of Science:
- Neuroscience
- Vascular Biology
- Biochemistry
Background:
- Amyloid-beta (A beta) peptides are implicated in Alzheimer's dementia pathophysiology.
- Cerebral circulation plays a critical role in brain function and is affected in dementia.
Purpose of the Study:
- To investigate the direct effects of A beta peptides on cerebral blood flow and vascular responses.
- To determine the role of reactive oxygen species in A beta-induced vascular dysfunction.
Main Methods:
- In vivo studies using anesthetized mice with cranial windows to monitor cerebral blood flow (CBF).
- Application of A beta 1-40 and analogs to cerebral vasculature.
- Assessment of vasoconstrictor responses to U-46619 and hypocapnia.
- Treatment with free radical scavengers and use of modified A beta peptides.
Main Results:
- Topical A beta 1-40 reduced resting CBF and augmented U-46619-induced vasoconstriction.
- A beta 1-40 effects were reversed by antioxidants and abolished by a mutation preventing free radical production.
- A beta 1-40 caused vasoconstriction in isolated cerebral arteries at nanomolar concentrations.
Conclusions:
- A beta peptides directly constrict cerebral arteries and enhance vasoconstrictor responses.
- A beta-induced production of reactive oxygen species is a key mechanism underlying these vascular effects.
- The vascular actions of A beta may contribute to cognitive decline in Alzheimer's dementia.