Mechanisms underlying the vascular activity of β-amyloid protein fragment (βA425–35) at the level of skin microvasculature

Khalil, Zeinab; Chen, Haibo; Helme, Robert D.

doi:10.1016/0006-8993(96)00685-3

Cited by 22 publications

(14 citation statements)

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“…We have reported that Aβ peptides induce vasoconstriction of the blood vessels and reduces endothelial mediated vascular responses [4][5][6][7]. These results have been confirmed in this study (Fig.…”

Section: Discussionsupporting

confidence: 93%

“…By monitoring changes in skin microvasculature, we have shown that Aβ peptides are capable of constricting the microvasculature via mechanisms that involve the release of endothelin and reactive oxygen species and we were able to reverse the vascular toxic effects of Aβ peptides using appropriate inhibitors [4][5][6][7]. Our results were later confirmed by other groups utilising isolated blood vessels or cerebral blood vessels [8][9][10][11][12].…”

Section: Introductionsupporting

confidence: 86%

“…Our group at the University of Melbourne, Australia, and others have provided strong evidence to support the notion that the changes in peripheral microvasculature in response Aβ peptides could mirror their actions in the cerebral vessels [4][5][6][7][8][9][10][11][12]. In the current study, we utilised the rat skin microvasculature to examine ability of AChE inhibitors to modulate the vascular toxic effects of Aβ peptides.…”

Section: Discussionmentioning

confidence: 71%

“…Khalil's group provided evidence that the mechanisms underlying the vasoconstrictive effects of Aβ involve the release of endothelin and reactive oxygen species [4][5][6][7]. That Donepezil at 10 µM and 100µM and Rivastigmine at 100µM concentration were capable of reducing the vasoconstrictive effects of Aβ peptides support the proposition that these drugs could be partly acting via modulating the mechanisms by which Aβ mediated vasoconstriction.…”

Section: Discussionmentioning

confidence: 72%

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Pharmacological Manipulation of the Vasoconstrictive Effects of Amyloid- β Peptides by Donepezil and Rivastigmine

Doganay

Khodr²,

Georgiou³

et al. 2006

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The amyloid-beta (Abeta) peptide has been linked to the pathology of Alzheimer's disease (AD). There is now evidence to support a vasoconstrictive effect of Abeta 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 Abeta25-35 and Abeta1-40. The ability of these drugs to improve endothelial mediated vascular responses to acetylcholine and bradykinin subsequent to perfusion of Abeta peptides was also investigated. The vascular responses to Abeta 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. Abeta25-35 (1 microM) and Abeta1-40 (0.1 microM) induced a vasoconstrictor effect and significantly reduced the vasodilator response to acetylcholine (100 microM) and bradykinin (1 microM). Donepezil (100 microM) and Rivastigmine (100 microM) both reduced the vasoconstrictor effect of Abeta 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 Abeta. The current study provides the first evidence in vivo to suggest that acetylcholinesterase inhibitors modulate the vasoconstrictive effects of Abeta peptides at the level of skin microvasculature. We raise the notion that Donepezil and Rivastigmine mediate these vascular modulatory effects via an action on Abeta-mediated vasoconstrictor mechanisms rather than an independent action on endothelial or smooth muscle cell mediated responses.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 72%

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Pharmacological Manipulation of the Vasoconstrictive Effects of Amyloid- β Peptides by Donepezil and Rivastigmine

Doganay

Khodr²,

Georgiou³

et al. 2006

CAR

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“…Aβ (25 -35) has a vasoconstrictor response at the level of the microvasculature operating through endothelin and protein kinase C [206]. This effect might also involve an interaction with calcitonin gene related polypeptide (CGRP), substance P, and the serpin enzyme complex (SEC) [202].…”

Section: In Vitro Studies: Aβmentioning

confidence: 99%

The Functions of the Amyloid Precursor Protein Gene and Its Derivative Peptides: II Experimental Evidence and Clinical Studies

Panegyres¹,

Atkins²

2011

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Endothelin and Free Radicals Modulate Microvascular Responses in Streptozotocin-Induced Diabetic Rats

Bassirat

Khalil

2000

Microvascular Research

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Mechanisms underlying the vascular activity of β-amyloid protein fragment (βA425–35) at the level of skin microvasculature

Cited by 22 publications

References 50 publications

Pharmacological Manipulation of the Vasoconstrictive Effects of Amyloid- β Peptides by Donepezil and Rivastigmine

Pharmacological Manipulation of the Vasoconstrictive Effects of Amyloid- β Peptides by Donepezil and Rivastigmine

The Functions of the Amyloid Precursor Protein Gene and Its Derivative Peptides: II Experimental Evidence and Clinical Studies

Endothelin and Free Radicals Modulate Microvascular Responses in Streptozotocin-Induced Diabetic Rats

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Mechanisms underlying the vascular activity of β-amyloid protein fragment (βA425–35) at the level of skin microvasculature

Cited by 22 publications

References 50 publications

Pharmacological Manipulation of the Vasoconstrictive Effects of Amyloid- &#946; Peptides by Donepezil and Rivastigmine

Pharmacological Manipulation of the Vasoconstrictive Effects of Amyloid- &#946; Peptides by Donepezil and Rivastigmine

The Functions of the Amyloid Precursor Protein Gene and Its Derivative Peptides: II Experimental Evidence and Clinical Studies

Endothelin and Free Radicals Modulate Microvascular Responses in Streptozotocin-Induced Diabetic Rats

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Pharmacological Manipulation of the Vasoconstrictive Effects of Amyloid- β Peptides by Donepezil and Rivastigmine

Pharmacological Manipulation of the Vasoconstrictive Effects of Amyloid- β Peptides by Donepezil and Rivastigmine