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(Stroke. 2001;32:1559.)
© 2001 American Heart Association, Inc.

Original Contributions

Enhanced Endothelium-Dependent Vasodilation in Fabry Disease

Gheona Altarescu, MD; David F. Moore, MD, PhD, DIC; Randall Pursley, MSEE; Umberto Campia, MD; Seth Goldstein, ScD; Melissa Bryant, RN; Julio A. Panza, MD Raphael Schiffmann, MD

From the Developmental and Metabolic Neurology Branch (G.A., D.F.M.), National Institute of Neurological Disorders and Stroke; the Cardiology Branch (U.C., M.B., J.A.P., R.S.), National Heart, Lung, and Blood Institute; the Center for Information Technology (R.P.); and the Office for Research Services (S.G.), National Institutes of Health, Bethesda, Md.

Correspondence to Raphael Schiffmann, MD, National Institutes of Health, Building 10, Room 3D03, 9000 Rockville Pike, Bethesda, MD 20892-1260. E-mailrs4e{at}nih.gov

Background and Purpose—Fabry disease is an X-linked lysosomal storage disease secondary to deficiency of -galactosidase A with resulting glycolipid accumulation, particularly globotriaosylceramide in arterial smooth muscle and endothelial cells. A systemic vasculopathy, including early-onset stroke, is prevalent without a clear pathogenesis.

Methods—Seventeen normotensive and normocholesterolemic hemizygous Fabry patients (aged 21 to 49 years) and 13 control subjects (aged 21 to 48 years) were investigated by venous plethysmography, allowing assessment of forearm blood flow. Plethysmographic measurements were obtained at baseline and during intra-arterial infusion of acetylcholine and sodium nitroprusside both with and without N^G-monomethyl-L-arginine (L-NMMA).

Results—Forearm blood flow was significantly higher in patients than in control subjects at all 3 acetylcholine doses (P=0.014). Patients had a greater response to acetylcholine even after the addition of L-NMMA (P=0.036).

Conclusions—These results demonstrate an increased endothelium-mediated vascular reactivity in Fabry disease. The increased vessel response to acetylcholine with and without L-NMMA suggests altered functionality of non-NO endothelium-dependent vasodilatory pathways.

Key Words: acetylcholine • blood flow • endothelium-derived relaxing factors • lipids • nitric oxide • vasodilation

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