TY - JOUR
T1 - Homocysteine impairs coronary microvascular dilator function in humans
AU - Tawakol, Ahmed
AU - Forgione, Marc A.
AU - Stuehlinger, Markus
AU - Alpert, Nathaniel M.
AU - Cooke, John P.
AU - Loscalzo, Joseph
AU - Fischman, Alan J.
AU - Creager, Mark A.
AU - Gewirtz, Henry
N1 - Funding Information:
This study was supported in part by grants from the NIH National Heart, Lung, and Blood Institute HL10107 (A. T.), HL48743 (M. A. C.), HL55993, HL58976, HL61795 (J. L.) and HL58638 (J. C.), the Cardiofellows Foundation (A. T.), the American Society of Nuclear Cardiology (A. T.) and the Tobacco Related Diseases Research Program (J. C.). Dr. Cooke is an Established Investigator of the American Heart Association. Dr. Stuehlinger is a recipient of an “Erwin Schroedinger Auslandsstipendium” provided by the Austrian “Fonds zur Foerderung der wissenschaftlichen Forschung” (J1893-MED)
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2002/9/18
Y1 - 2002/9/18
N2 - OBJECTIVES: We sought to use positron emission tomography (PET) to test the hypothesis that hyperhomocysteinemia adversely effects coronary microvascular dilator function. BACKGROUND: Hyperhomocysteinemia is associated with abnormal endothelium-dependent vasodilation in peripheral human arteries. However, its effect on the coronary, circulation is not known. METHODS: Eighteen healthy humans, age 24 to 56 years, were enrolled in a double-blind, crossover trial. Basal and adenosine-stimulated myocardial blood flow (MBF) was determined by PET: after ingestion of placebo and after methionine-induced hyperhomocysteinemia. Further, brachial ultrasonography was used to assess flow-mediated vasodilation. Additionally, to assess the role of nitric oxide (NO) in adenosine-mediated vasodilation, the MBF response to adenosine was measured in the presence and absence of the NO synthase antagonist NG-monomethyl-L-arginine (L-NMMA) (0.3 mg/kg/min intravenously). RESULTS: Hyperhomocysteinemia resulted in a reduction in the MBF dose-response curve to adenosine (p < 0.05). This was most apparent with low dose adenosine, where MBF augmentation was significantly blunted during hyperhomocysteinemia (1.06 ± 1.00 ml/min/g vs. 0.58 ± 0.78 ml/min/g, placebo vs. methionine, p < 0.05). Similarly, flow-mediated brachial artery vasodilation was impaired during hyperhomocysteinemia (4.4 ± 2.6% vs. 2.6 ± 2.3%, placebo vs. methionine, p < 0.05). In a separate series of experiments, MBF during adenosine was reduced in the presence of L-NMMA (p < 0.05 analysis of variance). This was most apparent at the low dose of adenosine, where MBF response to adenosine was blunted in the presence of L-NMMA (2.08 ± 1.34 ml/min/g vs. 1.48 ± 1.32 ml/min/g, placebo vs. L-NMMA, p < 0.05). CONCLUSIONS: The data, therefore, support the hypothesis that acute hyperhomocysteinemia impairs microvascular dilation in the human coronary circulation as a result of reduced NO bioavailability.
AB - OBJECTIVES: We sought to use positron emission tomography (PET) to test the hypothesis that hyperhomocysteinemia adversely effects coronary microvascular dilator function. BACKGROUND: Hyperhomocysteinemia is associated with abnormal endothelium-dependent vasodilation in peripheral human arteries. However, its effect on the coronary, circulation is not known. METHODS: Eighteen healthy humans, age 24 to 56 years, were enrolled in a double-blind, crossover trial. Basal and adenosine-stimulated myocardial blood flow (MBF) was determined by PET: after ingestion of placebo and after methionine-induced hyperhomocysteinemia. Further, brachial ultrasonography was used to assess flow-mediated vasodilation. Additionally, to assess the role of nitric oxide (NO) in adenosine-mediated vasodilation, the MBF response to adenosine was measured in the presence and absence of the NO synthase antagonist NG-monomethyl-L-arginine (L-NMMA) (0.3 mg/kg/min intravenously). RESULTS: Hyperhomocysteinemia resulted in a reduction in the MBF dose-response curve to adenosine (p < 0.05). This was most apparent with low dose adenosine, where MBF augmentation was significantly blunted during hyperhomocysteinemia (1.06 ± 1.00 ml/min/g vs. 0.58 ± 0.78 ml/min/g, placebo vs. methionine, p < 0.05). Similarly, flow-mediated brachial artery vasodilation was impaired during hyperhomocysteinemia (4.4 ± 2.6% vs. 2.6 ± 2.3%, placebo vs. methionine, p < 0.05). In a separate series of experiments, MBF during adenosine was reduced in the presence of L-NMMA (p < 0.05 analysis of variance). This was most apparent at the low dose of adenosine, where MBF response to adenosine was blunted in the presence of L-NMMA (2.08 ± 1.34 ml/min/g vs. 1.48 ± 1.32 ml/min/g, placebo vs. L-NMMA, p < 0.05). CONCLUSIONS: The data, therefore, support the hypothesis that acute hyperhomocysteinemia impairs microvascular dilation in the human coronary circulation as a result of reduced NO bioavailability.
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U2 - 10.1016/S0735-1097(02)02069-7
DO - 10.1016/S0735-1097(02)02069-7
M3 - Article
C2 - 12354427
AN - SCOPUS:0037130772
SN - 0735-1097
VL - 40
SP - 1051
EP - 1058
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 6
ER -