Published online before print June 29, 2006, doi: 10.1161/01.STR.0000231640.32543.11
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Stroke. 2006;37:2024.)
© 2006 American Heart Association, Inc.
Original Contributions |
ADMA Increases Arterial Stiffness and Decreases Cerebral Blood Flow in Humans
From the Departments of Nephrology (J.T.K., S.G., J.M., D.F.), Neuroradiology (F.D.), and Psychiatry (A.K.), Medical School, Hannover, and the Institute for Clinical Pharmacology (J.M.-L., F.S., S.M.B.-B.), Otto von Guericke Universität, Magdeburg, Germany, and the Division of Cardiovascular Medicine (J.T.K., J.P.C.), Stanford University School of Medicine, Stanford, Calif.
Correspondence to J. T. Kielstein, MD, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305-5406. E-mail adma{at}stanford.edu
Background and Purpose— Preclinical studies have revealed that the endogenous nitric oxide synthase inhibitor, asymmetric dimethylarginine (ADMA), increases vascular tone in cerebral blood vessels. Marked elevations of ADMA blood levels were found in patients with diseases characterized by decreased cerebral perfusion, such as ischemic stroke. Arterial stiffness is an independent predictor of stroke and other adverse cardiovascular events. The aim of this study was to investigate the influence of a systemic subpressor dose of ADMA on arterial stiffness and cerebral perfusion in humans.
Methods— Using a double-blind, vehicle-controlled study design, we allocated 20 healthy men in random order to infusion of either ADMA (0.10 mg ADMA/kg per min) or vehicle over a period of 40 minutes. Arterial stiffness was assessed noninvasively by pulse wave analysis. All volunteers underwent measurement of cerebral perfusion by dynamic contrast-enhanced perfusion magnetic resonance imaging of the brain.
Results— Infusion of ADMA significantly decreased total cerebral perfusion by 15.1±4.5% (P=0.007), whereas blood flow in the vehicle group increased by 7.7±2.8% (P=0.02). ADMA also increased arterial stiffness as assessed by measurement of the augmentation index (–12.6±1.9 to –9.6±1.5, P=0.007).
Conclusions— Our results document for the first time that subpressor doses of ADMA increase vascular stiffness and decrease cerebral perfusion in healthy subjects. Thus, ADMA is an important endogenous modulator of cerebral vascular tone and may be involved in the pathogenesis of cerebrovascular disease.
Key Words: cerebral blood flow • hemodynamics • nitric oxide • stroke, ischemic • vascular resistance
This article has been cited by other articles:
 |
|
 |
|
  A. Pikula, R. H. Boger, A. S. Beiser, R. Maas, C. DeCarli, E. Schwedhelm, J. J. Himali, F. Schulze, R. Au, M. Kelly-Hayes, et al. Association of Plasma ADMA Levels With MRI Markers of Vascular Brain Injury: Framingham Offspring Study Stroke, September 1, 2009; 40(9): 2959 - 2964. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Chirinos, R. David, J. A. Bralley, H. Zea-Diaz, E. Munoz-Atahualpa, F. Corrales-Medina, C. Cuba-Bustinza, J. Chirinos-Pacheco, and J. Medina-Lezama Endogenous Nitric Oxide Synthase Inhibitors, Arterial Hemodynamics, and Subclinical Vascular Disease: The PREVENCION Study Hypertension, December 1, 2008; 52(6): 1051 - 1059. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Williams The Year in Hypertension J. Am. Coll. Cardiol., May 6, 2008; 51(18): 1803 - 1817. [Full Text] [PDF]
|
|
|
|
|
|
H. Dayoub, R. N. Rodionov, C. Lynch, J. P. Cooke, E. Arning, T. Bottiglieri, S. R. Lentz, and F. M. Faraci Overexpression of Dimethylarginine Dimethylaminohydrolase Inhibits Asymmetric Dimethylarginine-Induced Endothelial Dysfunction in the Cerebral Circulation Stroke, January 1, 2008; 39(1): 180 - 184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Juonala, J. S.A. Viikari, G. Alfthan, J. Marniemi, M. Kahonen, L. Taittonen, T. Laitinen, and O. T. Raitakari Brachial Artery Flow-Mediated Dilation and Asymmetrical Dimethylarginine in the Cardiovascular Risk in Young Finns Study Circulation, September 18, 2007; 116(12): 1367 - 1373. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Duckelmann, F. Mittermayer, D. G. Haider, J. Altenberger, J. Eichinger, and M. Wolzt Asymmetric Dimethylarginine Enhances Cardiovascular Risk Prediction in Patients With Chronic Heart Failure Arterioscler Thromb Vasc Biol, September 1, 2007; 27(9): 2037 - 2042. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. G. Ingram, S. C. Newcomer, E. M. Price, K. E. Eklund, R. M. McAllister, and M. H. Laughlin Chronic nitric oxide synthase inhibition blunts endothelium-dependent function of conduit coronary arteries, not arterioles Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2798 - H2808. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. T. Kielstein and C. Zoccali A New Perspective for the Treatment of Renal Diseases? J. Am. Soc. Nephrol., May 1, 2007; 18(5): 1365 - 1367. [Full Text] [PDF]
|
|
|
|
|
|
J. Toth, A. Racz, P. M. Kaminski, M. S. Wolin, Z. Bagi, and A. Koller Asymmetrical Dimethylarginine Inhibits Shear Stress-Induced Nitric Oxide Release and Dilation and Elicits Superoxide-Mediated Increase in Arteriolar Tone Hypertension, March 1, 2007; 49(3): 563 - 568. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. T. Kielstein and J. P. Cooke Should We Measure Asymmetric Dimethylarginine in Patients with Coronary Artery Disease? Clin. Chem., February 1, 2007; 53(2): 161 - 163. [Full Text] [PDF]
|
|
|
|
|
|
K. Tsuda Asymmetric Dimethylarginine and Cerebrovascular Disorders in Humans Stroke, December 1, 2006; 37(12): 2870 - 2870. [Full Text] [PDF]
|
|