title: Characteristic features of in vivo skin microvascular reactivity in CADASIL.
abstract: CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is caused by mutations in the Notch3 receptor expressed at the surface of vascular smooth muscle cells. The functional consequences of the disease at the peripheral microcirculation level are incompletely elucidated. In this study, we aimed to assess, in vivo, the endothelium-dependent and independent vasodilation of the skin microvasculature in CADASIL patients. Twenty-three affected subjects were compared with 23 gender and age-matched controls. The brachial artery endothelium-dependent and endothelium-independent vasodilation were assessed after forearm cuff occlusion and nitroglycerin administration. Skin vasoreactivity to transcutaneous administration of acetylcholine and sodium nitroprussiate, and after postocclusive hyperemia were measured by Laser Doppler flowmetry. The maximum changes in the diameter of the brachial artery after the cuff release or after nitroglycerin administration did not differ between patients and controls. With iontopheresis, only the peak value of the dose response was found decreased in normocholesterolemic patients after nitroprussiate administration. The postocclusive test revealed a large increase of the time to peak value and whole duration of the hyperemic response in CADASIL patients. The results of this study show that the skin vasoreactivity is altered in CADASIL. Particularly, the kinetics of reactive hyperemia after cuff occlusion is dramatically changed with a lengthened and delayed response. This characteristic pattern may be related to the specific ultrastructural modifications related to Notch3 gene mutations involving smooth muscle cells in the microvasculature.
authors.affiliation: Department of Neurology, CHU Lariboisière, Assistance Publique des Hôpitaux de Paris, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Gobron
authors.forename: Katayoun
authors.initials: K
authors.lastname: Vahedi
authors.forename: Eric
authors.initials: E
authors.lastname: Vicaut
authors.forename: Olivier
authors.initials: O
authors.lastname: Stucker
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Laemmel
authors.forename: Nathalie
authors.initials: N
authors.lastname: Baudry
authors.forename: Marie Germaine
authors.initials: MG
authors.lastname: Bousser
authors.forename: Hugues
authors.initials: H
authors.lastname: Chabriat
mesh_terms: D000328:Adult; D000368:Aged; D001916:Brachial Artery / Q000502:physiology; D046589:CADASIL / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008833:Microcirculation / Q000502:physiology; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D012039:Regional Blood Flow / Q000502:physiology; D012867:Skin / Q000098:blood supply*; D014664:Vasodilation / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D009599:Nitroprusside