From Abteilung Kardiologie, Medizinische Hochschule Hannover, Hannover,
Germany.
Correspondence to Helmut Drexler, MD, Abteilung Kardiologie, Medizinische Hochschule Hannover, Carl-Neubergstr 1, 30625 Hannover, FRG.
Background—Chronic heart failure
(CHF) is associated with endothelial dysfunction
including impaired endothelium-mediated, flow-dependent
dilation (FDD). There is evidence for increased radical formation in
CHF, raising the possibility that nitric oxide is
inactivated by radicals, thereby impairing
endothelial function. To test this hypothesis, we
determined the effect of the antioxidant vitamin C on FDD in patients
with CHF.
Methods and Results—High-resolution ultrasound and Doppler
was used to measure radial artery diameter and blood flow in 15
patients with CHF and 8 healthy volunteers. Vascular effects of vitamin
C (25 mg/min IA) and placebo were determined at rest and during
reactive hyperemia (causing
endothelium-mediated dilation) before and after
intra-arterial infusion of
N-monomethyl-L-arginine (L-NMMA) to
inhibit endothelial synthesis of nitric oxide. Vitamin
C restored FDD in patients with heart failure after acute
intra-arterial administration (13.2±1.7% versus
8.2±1.0%; P<.01) and after 4 weeks of oral therapy
(11.9±0.9% versus 8.2±1.0%; P<.05). In particular,
the portion of FDD mediated by nitric oxide (ie, inhibited by L-NMMA)
was increased after acute as well as after chronic treatment (CHF
baseline: 4.2±0.7%; acute: 9.1±1.3%; chronic: 7.3±1.2%; normal
subjects: 8.9±0.8%; P<.01).
Conclusions—Vitamin C improves FDD in patients with CHF as the
result of increased availability of nitric oxide. This observation
supports the concept that endothelial dysfunction in
patients with CHF is, at least in part, due to accelerated degradation
of nitric oxide by radicals.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Vitamin C Improves Endothelial Function of Conduit Arteries in Patients With Chronic Heart Failure
Key Words: endothelium • antioxidants • vasoconstriction • vasodilation
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U. Landmesser, R. Merten, S. Spiekermann, K. Buttner, H. Drexler, and B. Hornig Vascular Extracellular Superoxide Dismutase Activity in Patients With Coronary Artery Disease : Relation to Endothelium-Dependent Vasodilation Circulation, May 16, 2000; 101(19): 2264 - 2270. [Abstract] [Full Text] [PDF]
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O. T. Raitakari, M. R. Adams, R. J. McCredie, K. A. Griffiths, R. Stocker, and D. S. Celermajer Oral vitamin C and endothelial function in smokers: short-term improvement, but no sustained beneficial effect J. Am. Coll. Cardiol., May 1, 2000; 35(6): 1616 - 1621. [Abstract] [Full Text] [PDF]
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D. L. Sherman, J. F. Keaney Jr, E. S. Biegelsen, S. J. Duffy, J. D. Coffman, and J. A. Vita Pharmacological Concentrations of Ascorbic Acid Are Required for the Beneficial Effect on Endothelial Vasomotor Function in Hypertension Hypertension, April 1, 2000; 35(4): 936 - 941. [Abstract] [Full Text] [PDF]
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 B. Frei On the Role of Vitamin C and Other Antioxidants in Atherogenesis and Vascular Dysfunction Experimental Biology and Medicine, December 1, 1999; 222(3): 196 - 204. [Abstract] [Full Text]
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 D. Tousoulis, G. Davies, and P. Toutouzas Vitamin C Increases Nitric Oxide Availability in Coronary Atherosclerosis Ann Intern Med, July 20, 1999; 131(2): 156 - 157. [Full Text] [PDF]
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T. Munzel and D. G. Harrison Increased Superoxide in Heart Failure : A Biochemical Baroreflex Gone Awry Circulation, July 20, 1999; 100(3): 216 - 218. [Full Text] [PDF]
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J. Bauersachs, A. Bouloumie, D. Fraccarollo, K. Hu, R. Busse, and G. Ertl Endothelial Dysfunction in Chronic Myocardial Infarction Despite Increased Vascular Endothelial Nitric Oxide Synthase and Soluble Guanylate Cyclase Expression : Role of Enhanced Vascular Superoxide Production Circulation, July 20, 1999; 100(3): 292 - 298. [Abstract] [Full Text] [PDF]
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N. Gokce, J. F. Keaney Jr, B. Frei, M. Holbrook, M. Olesiak, B. J. Zachariah, C. Leeuwenburgh, J. W. Heinecke, and J. A. Vita Long-Term Ascorbic Acid Administration Reverses Endothelial Vasomotor Dysfunction in Patients With Coronary Artery Disease Circulation, June 29, 1999; 99(25): 3234 - 3240. [Abstract] [Full Text] [PDF]
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R. Varin, P. Mulder, V. Richard, F. Tamion, C. Devaux, J.-P. Henry, F. Lallemand, G. Lerebours, and C. Thuillez Exercise Improves Flow-Mediated Vasodilatation of Skeletal Muscle Arteries in Rats With Chronic Heart Failure : Role of Nitric Oxide, Prostanoids, and Oxidant Stress Circulation, June 8, 1999; 99(22): 2951 - 2957. [Abstract] [Full Text] [PDF]
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A. C Carr and B. Frei Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans Am. J. Clinical Nutrition, June 1, 1999; 69(6): 1086 - 1107. [Abstract] [Full Text] [PDF]
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W. G. Mayhan and G. M. Sharpe Chronic exposure to nicotine alters endothelium-dependent arteriolar dilatation: effect of superoxide dismutase J Appl Physiol, April 1, 1999; 86(4): 1126 - 1134. [Abstract] [Full Text] [PDF]
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 R. Heller, F. Munscher-Paulig, R. Grabner, and U. Till L-Ascorbic Acid Potentiates Nitric Oxide Synthesis in Endothelial Cells J. Biol. Chem., March 19, 1999; 274(12): 8254 - 8260. [Abstract] [Full Text] [PDF]
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B. Hornig, N. Arakawa, D. Haussmann, and H. Drexler Differential Effects of Quinaprilat and Enalaprilat on Endothelial Function of Conduit Arteries in Patients With Chronic Heart Failure Circulation, December 22, 1998; 98(25): 2842 - 2848. [Abstract] [Full Text]
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H. Drexler Endothelium as a Therapeutic Target in Heart Failure Circulation, December 15, 1998; 98(24): 2652 - 2655. [Full Text] [PDF]
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 T. S. Jackson, A. Xu, J. A. Vita, and J. F. Keaney Jr Ascorbate Prevents the Interaction of Superoxide and Nitric Oxide Only at Very High Physiological Concentrations Circ. Res., November 2, 1998; 83(9): 916 - 922. [Abstract] [Full Text] [PDF]
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A. Huang, J. A. Vita, R. C. Venema, and J. F. Keaney Jr. Ascorbic Acid Enhances Endothelial Nitric-oxide Synthase Activity by Increasing Intracellular Tetrahydrobiopterin J. Biol. Chem., June 2, 2000; 275(23): 17399 - 17406. [Abstract] [Full Text] [PDF]
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R. Heller, A. Unbehaun, B. Schellenberg, B. Mayer, G. Werner-Felmayer, and E. R. Werner L-Ascorbic Acid Potentiates Endothelial Nitric Oxide Synthesis via a Chemical Stabilization of Tetrahydrobiopterin J. Biol. Chem., January 5, 2001; 276(1): 40 - 47. [Abstract] [Full Text] [PDF]
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S. Mak, Z. Egri, G. Tanna, R. Colman, and G. E. Newton Vitamin C prevents hyperoxia-mediated vasoconstriction and impairment of endothelium-dependent vasodilation Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2414 - H2421. [Abstract] [Full Text] [PDF]
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V. A. Tyurin, S.-X. Liu, Y. Y. Tyurina, N. B. Sussman, C. A. Hubel, J. M. Roberts, R. N. Taylor, and V. E. Kagan Elevated Levels of S-Nitrosoalbumin in Preeclampsia Plasma Circ. Res., June 8, 2001; 88(11): 1210 - 1215. [Abstract] [Full Text] [PDF]
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