Abstract
The amyloid-b (Aβ) peptide has been linked to the pathology of Alzheimers disease (AD). There is now evidence to support a vasoconstrictive effect of Aβ protein that could be detected in peripheral skin microvasculature. In this study we investigated the ability of acetylcholinesterase (AChE) inhibitors, Donepezil and Rivastigmine, to modulate the vasoconstrictor activity of Aβ25-35 and Aβ1-40. The ability of these drugs to improve endothelial mediated vascular responses to acetylcholine and bradykinin subsequent to perfusion of Aβ peptides was also investigated. The vascular responses to Aβ peptides, acetylcholine, bradykinin and sodium nitroprusside and their modulation by acetylcholinesterase inhibitors were examined in the base of a vacuum induced blister raised on the rat hind footpad using laser Doppler flowmetry. Aβ25-35 (1μM) and Aβ1-40 (0.1μM) induced a vasoconstrictor effect and significantly reduced the vasodilator response to acetylcholine (100μM) and bradykinin (1μM). Donepezil (100μM) and Rivastigmine (100μM) both reduced the vasoconstrictor effect of Aβ peptides, and significantly restored the endothelial vascular response to acetylcholine. Similarly, Donepezil significantly restored the endothelial vascular response to bradykinin. The results also showed that the actions of acetylcholinesterase inhibitors are independent of a direct action on smooth muscle cell reactivity or on endothelial cell function in the absence of Aβ. The current study provides the first evidence in vivo to suggest that acetylcholinesterase inhibitors modulate the vasoconstrictive effects of Aβ peptides at the level of skin microvasculature. We raise the notion that Donepezil and Rivastigmine mediate these vascular modulatory effects via an action on Aβ-mediated vasoconstrictor mechanisms rather than an independent action on endothelial or smooth muscle cell mediated responses.
Keywords: Alzheimer's disease, Aβ peptides, acetylcholinesterase inhibitors, endothelial-dependent vasodilators, skin microvasculature
Current Alzheimer Research
Title: Pharmacological Manipulation of the Vasoconstrictive Effects of Amyloid- β Peptides by Donepezil and Rivastigmine
Volume: 3 Issue: 2
Author(s): Goksel Doganay, Bereha Khodr, George Georgiou and Zeinab Khalil
Affiliation:
Keywords: Alzheimer's disease, Aβ peptides, acetylcholinesterase inhibitors, endothelial-dependent vasodilators, skin microvasculature
Abstract: The amyloid-b (Aβ) peptide has been linked to the pathology of Alzheimers disease (AD). There is now evidence to support a vasoconstrictive effect of Aβ protein that could be detected in peripheral skin microvasculature. In this study we investigated the ability of acetylcholinesterase (AChE) inhibitors, Donepezil and Rivastigmine, to modulate the vasoconstrictor activity of Aβ25-35 and Aβ1-40. The ability of these drugs to improve endothelial mediated vascular responses to acetylcholine and bradykinin subsequent to perfusion of Aβ peptides was also investigated. The vascular responses to Aβ peptides, acetylcholine, bradykinin and sodium nitroprusside and their modulation by acetylcholinesterase inhibitors were examined in the base of a vacuum induced blister raised on the rat hind footpad using laser Doppler flowmetry. Aβ25-35 (1μM) and Aβ1-40 (0.1μM) induced a vasoconstrictor effect and significantly reduced the vasodilator response to acetylcholine (100μM) and bradykinin (1μM). Donepezil (100μM) and Rivastigmine (100μM) both reduced the vasoconstrictor effect of Aβ peptides, and significantly restored the endothelial vascular response to acetylcholine. Similarly, Donepezil significantly restored the endothelial vascular response to bradykinin. The results also showed that the actions of acetylcholinesterase inhibitors are independent of a direct action on smooth muscle cell reactivity or on endothelial cell function in the absence of Aβ. The current study provides the first evidence in vivo to suggest that acetylcholinesterase inhibitors modulate the vasoconstrictive effects of Aβ peptides at the level of skin microvasculature. We raise the notion that Donepezil and Rivastigmine mediate these vascular modulatory effects via an action on Aβ-mediated vasoconstrictor mechanisms rather than an independent action on endothelial or smooth muscle cell mediated responses.
Export Options
About this article
Cite this article as:
Doganay Goksel, Khodr Bereha, Georgiou George and Khalil Zeinab, Pharmacological Manipulation of the Vasoconstrictive Effects of Amyloid- β Peptides by Donepezil and Rivastigmine, Current Alzheimer Research 2006; 3 (2) . https://dx.doi.org/10.2174/156720506776383086
DOI https://dx.doi.org/10.2174/156720506776383086 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
GSK-3 Inhibitors: A New Class of Drugs for Alzheimer’s Disease Treatment
Current Drug Targets Therapeutic Targets in Extracellular Protein Deposition Diseases
Current Medicinal Chemistry Myalgic Encephalomyelitis: Symptoms and Biomarkers
Current Neuropharmacology Synthesis and Biological Interest of Structured Docosahexaenoic Acid–Containing Triacylglycerols and Phospholipids
Current Organic Chemistry Does Religiosity Protect Against Cognitive and Behavioral Decline in Alzheimers Dementia?
Current Alzheimer Research Protein Aggregation: Elucidation of the Mechanism and Determination of Associated Thermodynamic and Kinetic Parameters
Current Physical Chemistry Role of Methylene Blue in Trauma Neuroprotection and Neuropsychiatric Diseases
CNS & Neurological Disorders - Drug Targets Glycogen Synthase Kinase-3: A Potential Target for Drug Discovery in the Treatment of Neurodegenerative Disorders
Current Enzyme Inhibition Protective Effect of Vitamin B Therapy on Bone and Cardiovascular Disease
Recent Patents on Cardiovascular Drug Discovery Estrogen and Cytokines Production - The Possible Cause of Gender Differences in Neurological Diseases
Current Pharmaceutical Design Kinematic and Pressure Features of Handwriting and Drawing: Preliminary Results Between Patients with Mild Cognitive Impairment, Alzheimer Disease and Healthy Controls
Current Alzheimer Research Astrocytes: From the Physiology to the Disease
Current Alzheimer Research The Role of Matrix Metalloproteinases in Diabetes Mellitus
Current Topics in Medicinal Chemistry Metabolic Dysfunction in Alzheimers Disease and Related Neurodegenerative Disorders
Current Alzheimer Research Characteristics of Insulin-degrading Enzyme in Alzheimer's Disease: A Meta-Analysis
Current Alzheimer Research Pathways of Acetylcholine Synthesis, Transport and Release as Targets for Treatment of Adult-Onset Cognitive Dysfunction
Current Medicinal Chemistry Lack of Association between Genetic Polymorphism of Circadian Genes (PER2, PER3, CLOCK and OX2R) with Late Onset Depression and Alzheimer's Disease in a Sample of a Brazilian Population (Circadian Genes, Late-Onset Depression and Alzheimer's Disease)
Current Alzheimer Research Analysis of Functional Brain Images Using Population-Based Probabilistic Atlas
Current Medical Imaging Subduing the Green-eyed Monster: Bridging the Psychopharmacological and Psychosocial Treatment Perspective in Understanding Pathological Jealousy
Current Drug Targets New Vessel Formation in the Central Nervous System During Tumor Growth, Vascular Malformations, and Moyamoya
Current Neurovascular Research