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
-
Increased Prevalence of Vestibular Loss in Mild Cognitive Impairment and Alzheimer’s Disease
Current Alzheimer Research Emerging Evidence for the Role of Neurotransmitters in the Modulation of T Cell Responses to Cognate Ligands
Central Nervous System Agents in Medicinal Chemistry Pharmacological Management Options to Prevent and Reduce Ischemic Hemorrhagic Transformation
Current Drug Targets Treatment of Alzheimer's Disease: Classical Therapeutic Approach
Current Pharmaceutical Analysis The Role of Monocytes and Macrophages in the Pathogenesis of HIV-1 Infection
Current Medicinal Chemistry Retrospective Results on the Treatment of Chronic Hepatitis C with Different Interferon Regimes in a General Hospital
Current Drug Therapy Amyloid-β Peptides, Alzheimer's Disease and the Blood-brain Barrier
Current Alzheimer Research TiO2-Nanowired Delivery of Mesenchymal Stem Cells Thwarts Diabetes- Induced Exacerbation of Brain Pathology in Heat Stroke: An Experimental Study in the Rat Using Morphological and Biochemical Approaches
CNS & Neurological Disorders - Drug Targets Current Status of Hormone Replacement Therapy in Post Menopausal Women
Current Drug Therapy Reserve Mechanisms in Neurodegenerative Diseases: From Bench to Bedside and Back Again
Current Medicinal Chemistry Recent Developments in the Understanding and Treatment of Neurodegenerative Disorders Involving Protein Conformational Misfolding and Amyloid Formation
Medicinal Chemistry Reviews - Online (Discontinued) On the Interaction of β-Amyloid Peptides and α7-Nicotinic Acetylcholine Receptors in Alzheimer’s Disease
Current Alzheimer Research Meet Our Editorial Board Member
Current Alzheimer Research Pleiotropic Effects of Omega-3 Fatty Acids
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery α-Lipoic Acid Supplementation: A Tool for Obesity Therapy?
Current Pharmaceutical Design Advanced Nanomedicines for the Treatment and Diagnosis of Myocardial Infarction and Heart Failure
Current Drug Targets The Role of Vascular Factors in Late-Onset Sporadic Alzheimers Disease. Genetic and Molecular Aspects
Current Alzheimer Research New Therapeutic Applications of Phosphodiesterase 5 Inhibitors (PDE5-Is)
Current Medicinal Chemistry Visual and Quantitative Assessment of COVID-19 Pneumonia on Chest CT: The Relationship with Disease Severity and Clinical Findings
Current Medical Imaging Common Variants in Toll-Like Receptor 4 Confer Susceptibility to Alzheimer’s Disease in a Han Chinese Population
Current Alzheimer Research