Document Detail

Enhanced L-arginine-induced vasoreactivity suggests endothelial dysfunction in CADASIL.
MedLine Citation:
PMID:  18537053     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Mutations in the Notch3 gene are the cause of CADASIL, a hereditary small vessel disease leading to stroke and vascular dementia. The disease is characterized by ultrastructural granular deposits within small arterial vessels and degeneration of vascular smooth muscle cells. Yet, little is known about endothelial function in CADASIL. Vasoreactivity induced by L-arginine, which is the substrate for endothelial nitric oxide synthase, is a parameter of endothelial function and has been shown to be altered in patients with cerebrovascular disease. METHODS: To assess endothelial function in CADASIL, L-arginine-induced vasoreactivity was studied in 25 CADASIL subjects and 24 non-CADASIL control subjects without previous history of cerebrovascular disease by transcranial Doppler sonography of the middle cerebral artery. RESULTS: Resting mean flow velocity was significantly reduced in patients (43.7 +/- 14.5 cm/s) compared to controls (57.0 +/- 10.4 cm/s) [p < 0.001]. Patients exhibited a significantly higher pulsatility index (PI = 0.94 +/- 0.19) than control subjects (PI = 0.79 +/- 0.11) [p < 0.01]. L-arginine-induced vasoreactivity was significantly increased in patients (36.1 +/- 15.5 % ) versus controls (27.9 +/- 8.5 %) [p < 0.05]. In patients, there was a significant reduction of the PI following L-arginine application (PI = 0.86 +/- 0.13) compared to resting PI [p < 0.01]. CONCLUSIONS: Our results may indicate a pathogenic role of impaired cerebral hemodynamics and endothelial dysfunction in CADASIL. Our finding of enhanced L-arginine vasoreactivity might have therapeutic implications for CADASIL and sporadic small vessel disease.
Nils Peters; Tobias Freilinger; Christian Opherk; Thomas Pfefferkorn; Martin Dichgans
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Publication Detail:
Type:  Controlled Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-06-13
Journal Detail:
Title:  Journal of neurology     Volume:  255     ISSN:  0340-5354     ISO Abbreviation:  J. Neurol.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-12-23     Completed Date:  2009-04-14     Revised Date:  2010-03-23    
Medline Journal Info:
Nlm Unique ID:  0423161     Medline TA:  J Neurol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1203-8     Citation Subset:  IM    
Dept. of Neurology, Klinikum Grosshadern, Ludwig-Maximilians-University, Marchioninistrasse 15, 81377, Munich, Germany.
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MeSH Terms
Arginine / diagnostic use,  pharmacology*
Blood Flow Velocity / drug effects,  physiology
Blood Pressure / drug effects
CADASIL / complications,  genetics,  pathology*,  physiopathology
Cerebrovascular Circulation / drug effects*,  physiology
Endothelium / drug effects*,  pathology*
Heart Rate / drug effects
Middle Aged
Middle Cerebral Artery / drug effects,  ultrasonography
Receptors, Notch / genetics
Severity of Illness Index
Ultrasonography, Doppler, Transcranial / methods
Vascular Diseases / etiology
Reg. No./Substance:
0/NOTCH3 protein, human; 0/Receptors, Notch; 74-79-3/Arginine

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