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Impaired Endothelial Function of Forearm Resistance Arteries in CADASIL Patients
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
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2007 (English)In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 38, no 10, 2692-2697 p.Article in journal (Refereed) Published
Abstract [en]

Background and Purpose-Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary arteriopathy, which mainly involves the brain causing stroke and dementia. Mice expressing the mutated protein display early dysfunction in vasoreactivity in resistance arteries, but studies of patients have been inconclusive so far. Methods-We examined peripheral endothelium-dependent vasodilatation in 10 CADASIL-patients and 20 controls using 3 methods: venous occlusion plethysmography of forearm blood flow with intraarterial acetylcholine and sodium nitroprusside infusions for evaluation of resistance arteries, ultrasound with flow mediated vasodilatation (FMD) of the brachial artery for evaluation of a conduit artery, and the pulse wave method with measurements before and after terbutaline for evaluation of systemic endothelium-dependent vasodilation. Results-The CADASIL patients displayed reductions in both basal (P=0.034) and stimulated blood flow (P=0.023 for the highest dose of acetylcholine) and an impaired endothelium-dependent vasodilation when investigated in forearm resistance arteries (P=0.019). The FMD and the pulse wave method did not show any reduction in endothelium-dependent vasodilation in the patients. Conclusions-Endothelium-dependent vasodilation was impaired in resistance arteries, but not in a conduit artery, in the forearm of CADASIL patients.

Place, publisher, year, edition, pages
2007. Vol. 38, no 10, 2692-2697 p.
Keyword [en]
CADASIL syndrome, endothelium, vasodilation
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-96701DOI: 10.1161/STROKEAHA.107.490029ISI: 000249694900014PubMedID: 17761910OAI: oai:DiVA.org:uu-96701DiVA: diva2:171361
Available from: 2008-02-08 Created: 2008-02-08 Last updated: 2011-01-26Bibliographically approved
In thesis
1. Vascular Dysfunction in Stroke and CADASIL
Open this publication in new window or tab >>Vascular Dysfunction in Stroke and CADASIL
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cerebrovascular disease (CVD) is strongly linked to hypertension and generally occurs later in life than coronary artery disease (CAD). Three quarters of the patients with symptomatic CVD are above 65 years of age. The risk factors are the same for CVD and CAD, but the relative importance of the vascular risk factors differs greatly.

Genetic causes of stroke are relatively rare. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a hereditary disease which causes CVD in young adults and middle-aged people, with migraine, stroke, psychiatric illness and dementia as clinical manifestations.

The subject of this thesis is vascular function in stroke and CADASIL. Endothelium-dependent vasodilation (EDV) and arterial stiffness were investigated by different methods in stroke patients and CADASIL patients compared with healthy controls. Venous occlusion plethysmography with intra-arterial acetylcholine was used to evaluate EDV in the forearm resistance vessels. Flow-mediated vasodilation of the brachial artery was used to evaluate EDV in a conduit artery. Stroke patients displayed reduced EDV in resistance vessels compared with a healthy control group, but this reduction was not significant when, in a larger group of stroke patients, adjustments were made for blood pressure, antihypertensive treatment and other risk factors. Flow mediated vasodilation of the brachial artery was reduced in the stroke patients even after adjustment for risk factors.

Compared with controls, the CADASIL patients showed similar EDV in the conduit artery, but reduced EDV in resistance vessels.

Arterial compliance was evaluated by augmentation index from pulse wave analysis, by a ratio of cardiac stroke volume and pulse pressure, and by the distensibility of the carotid artery in relation to pulse pressure. Stroke patients and CADASIL patients did not display any significant increase in arterial stiffness when evaluated by these methods.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 51 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 308
Keyword
Internal medicine, stroke, CADASIL, endothelium, vasodilation, Invärtesmedicin
Identifiers
urn:nbn:se:uu:diva-8427 (URN)978-91-554-7081-4 (ISBN)
Public defence
2008-02-29, Enghoffsalen, Akademiska sjukhuset, ing 50, Uppsala, 09:15
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Available from: 2008-02-08 Created: 2008-02-08Bibliographically approved

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Stenborg, AnnaKalimo, HannuTerént, AndreasLind, Lars

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