Circulation, Vol 89, 2176-2182, Copyright © 1994 by American Heart Association
PS Tsao, LM McEvoy, H Drexler, EC Butcher and JP Cooke
BACKGROUND: We have shown that chronic administration of the nitric oxide
(NO) precursor L-arginine normalizes NO-dependent vasodilation and markedly
inhibits atherogenesis in a hypercholesterolemic rabbit model. We
hypothesized that this antiatherogenic effect is due to modulation of
endothelial adhesiveness by endothelium-derived NO. METHODS AND RESULTS:
New Zealand White rabbits were fed normal chow (Cont), a high-cholesterol
diet (Chol), a high-cholesterol diet supplemented with L-arginine (Arg), or
a normal diet supplemented with the NO synthase antagonist L-nitroarginine
(L-NA) for 2 weeks. In additional studies, some animals receiving L-NA were
also treated with hydralazine to normalize blood pressure. After 2 weeks,
thoracic aortas were harvested, opened longitudinally, and placed in a
culture dish with the endothelial surface exposed to medium containing WEHI
78/24 cells, a monocytoid cell line. After incubation with the monocytoid
cells for 30 minutes on a rocking platform, the aortic segments were washed
repeatedly to remove nonadherent cells and adherent cells counted by
epifluorescent microscopy. Monocytoid cell binding to aortic endothelium
was significantly increased in Chol (P < .001 versus Cont); binding was
markedly reduced in arginine-fed hypercholesterolemic animals (P < .05,
Arg versus Chol). Monocytoid cell binding to aortic endothelium was also
significantly increased in L-NA (P < .05); hydralazine normalized blood
pressure but did not reduce monocytoid cell binding. To confirm that
alterations in NO activity modulate endothelial cell-monocyte interaction,
the release of nitrogen oxides (NOx) by thoracic aortas was assessed by a
chemiluminescent technique. The concentration of NOx in the conditioned
medium from segments of Arg thoracic aortas was significantly greater than
that from Cont aortas, whereas that from L-NA aortas was significantly
less. CONCLUSIONS: Hypercholesterolemia enhances the adhesiveness of aortic
endothelium for monocytes; this effect is attenuated by dietary L-arginine.
Conversely, inhibition of NO synthesis enhances monocyte binding. The
results suggest that endothelium-derived NO plays an important role in
regulating the endothelial adhesiveness for monocytes. Alterations in NO
activity may play a critical role in atherogenesis.
ARTICLES
Enhanced endothelial adhesiveness in hypercholesterolemia is attenuated by L-arginine
Division of Cardiovascular Medicine, Stanford University School of Medicine, Calif. 94305.
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H. Miyazaki, H. Matsuoka, J. P. Cooke, M. Usui, S. Ueda, S. Okuda, and T. Imaizumi Endogenous Nitric Oxide Synthase Inhibitor : A Novel Marker of Atherosclerosis Circulation, March 9, 1999; 99(9): 1141 - 1146. [Abstract] [Full Text] [PDF]
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D. Corseaux, T. Le Tourneau, I. Six, M. D. Ezekowitz, E. P. Mc Fadden, T. Meurice, P. Asseman, C. Bauters, and B. Jude Enhanced Monocyte Tissue Factor Response After Experimental Balloon Angioplasty in Hypercholesterolemic Rabbit: Inhibition With Dietary L-Arginine Circulation, October 27, 1998; 98(17): 1776 - 1782. [Abstract] [Full Text] [PDF]
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H. Tomita, K. Egashira, M. Kubo-Inoue, M. Usui, M. Koyanagi, H. Shimokawa, M. Takeya, T. Yoshimura, and A. Takeshita Inhibition of NO Synthesis Induces Inflammatory Changes and Monocyte Chemoattractant Protein-1 Expression in Rat Hearts and Vessels Arterioscler Thromb Vasc Biol, September 1, 1998; 18(9): 1456 - 1464. [Abstract] [Full Text] [PDF]
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H.-B. Peng, M. Spiecker, and J. K. Liao Inducible Nitric Oxide: An Autoregulatory Feedback Inhibitor of Vascular Inflammation J. Immunol., August 15, 1998; 161(4): 1970 - 1976. [Abstract] [Full Text] [PDF]
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 J. K. Liao Endothelium and acute coronary syndromes Clin. Chem., August 1, 1998; 44(8): 1799 - 1808. [Abstract] [Full Text] [PDF]
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A. J. Maxwell, E. Schauble, D. Bernstein, and J. P. Cooke Limb Blood Flow During Exercise Is Dependent on Nitric Oxide Circulation, July 28, 1998; 98(4): 369 - 374. [Abstract] [Full Text] [PDF]
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R. Scalia, J. Z. Appel III, and A. M. Lefer Leukocyte-Endothelium Interaction During the Early Stages of Hypercholesterolemia in the Rabbit : Role of P-Selectin, ICAM-1, and VCAM-1 Arterioscler Thromb Vasc Biol, July 1, 1998; 18(7): 1093 - 1100. [Abstract] [Full Text] [PDF]
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P. S. Tsao, J. Niebauer, R. Buitrago, P. S. Lin, B.-y. Wang, J. P. Cooke, Y-d. Ida Chen, and G. M. Reaven Interaction of Diabetes and Hypertension on Determinants of Endothelial Adhesiveness Arterioscler Thromb Vasc Biol, June 1, 1998; 18(6): 947 - 953. [Abstract] [Full Text] [PDF]
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N. R. Harris and K. W. Langlois Age-dependent responses of the mesenteric vasculature to ischemia-reperfusion Am J Physiol Heart Circ Physiol, May 1, 1998; 274(5): H1509 - H1515. [Abstract] [Full Text] [PDF]
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U. Laufs, V. La Fata, J. Plutzky, and J. K. Liao Upregulation of Endothelial Nitric Oxide Synthase by HMG CoA Reductase Inhibitors Circulation, March 31, 1998; 97(12): 1129 - 1135. [Abstract] [Full Text] [PDF]
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G. Theilmeier, J. R. Chan, C. Zalpour, B. Anderson, B.-y. Wang, A. Wolf, P. S. Tsao, and J. P. Cooke Adhesiveness of Mononuclear Cells in Hypercholesterolemic Humans Is Normalized by Dietary L-Arginine Arterioscler Thromb Vasc Biol, December 1, 1997; 17(12): 3557 - 3564. [Abstract] [Full Text]
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L. M. McEvoy, M. A. Jutila, P. S. Tsao, J. P. Cooke, and E. C. Butcher Anti-CD43 Inhibits Monocyte-Endothelial Adhesion in Inflammation and Atherogenesis Blood, November 1, 1997; 90(9): 3587 - 3594. [Abstract] [Full Text] [PDF]
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M. Kimura, I. Kurose, J. Russell, and D. N. Granger Effects of Fluvastatin on Leukocyte–Endothelial Cell Adhesion in Hypercholesterolemic Rats Arterioscler Thromb Vasc Biol, August 1, 1997; 17(8): 1521 - 1526. [Abstract] [Full Text]
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Y. Mitani, K. Maruyama, and M. Sakurai Prolonged Administration of L-Arginine Ameliorates Chronic Pulmonary Hypertension and Pulmonary Vascular Remodeling in Rats Circulation, July 15, 1997; 96(2): 689 - 697. [Abstract] [Full Text]
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S. J. Hutchison, M. S. Reitz, K. Sudhir, R. E. Sievers, B.-Q. Zhu, Y.-P. Sun, T. M. Chou, P. C. Deedwania, K. Chatterjee, S. A. Glantz, et al. Chronic Dietary L-Arginine Prevents Endothelial Dysfunction Secondary to Environmental Tobacco Smoke in Normocholesterolemic Rabbits Hypertension, May 1, 1997; 29(5): 1186 - 1191. [Abstract] [Full Text]
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S. P. Schwarzacher, T. T. Lim, B. Wang, R. S. Kernoff, J. Niebauer, J. P. Cooke, and A. C. Yeung Local Intramural Delivery of L-Arginine Enhances Nitric Oxide Generation and Inhibits Lesion Formation After Balloon Angioplasty Circulation, April 1, 1997; 95(7): 1863 - 1869. [Abstract] [Full Text]
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A. M. Lefer Nitric Oxide: Nature's Naturally Occurring Leukocyte Inhibitor Circulation, February 4, 1997; 95(3): 553 - 554. [Full Text]
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M. R. Adams, W. Jessup, D. Hailstones, and D. S. Celermajer L-Arginine Reduces Human Monocyte Adhesion to Vascular Endothelium and Endothelial Expression of Cell Adhesion Molecules Circulation, February 4, 1997; 95(3): 662 - 668. [Abstract] [Full Text]
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J. P. Cooke and P. S. Tsao Arginine: A New Therapy for Atherosclerosis? Circulation, January 21, 1997; 95(2): 311 - 312. [Full Text]
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W. Aji, S. Ravalli, M. Szabolcs, X.-c. Jiang, R. R. Sciacca, R. E. Michler, and P. J. Cannon L-Arginine Prevents Xanthoma Development and Inhibits Atherosclerosis in LDL Receptor Knockout Mice Circulation, January 21, 1997; 95(2): 430 - 437. [Abstract] [Full Text]
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X.-F. Niu, G. Ibbotson, and P. Kubes A Balance Between Nitric Oxide and Oxidants Regulates Mast Cell–Dependent Neutrophil–Endothelial Cell Interactions Circ. Res., November 1, 1996; 79(5): 992 - 999. [Abstract] [Full Text]
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P. S. Tsao, R. Buitrago, J. R. Chan, and J. P. Cooke Fluid Flow Inhibits Endothelial Adhesiveness: Nitric Oxide and Transcriptional Regulation of VCAM-1 Circulation, October 1, 1996; 94(7): 1682 - 1689. [Abstract] [Full Text]
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S. Taddei, A. Virdis, L. Ghiadoni, P. Mattei, I. Sudano, G. Bernini, S. Pinto, and A. Salvetti Menopause Is Associated With Endothelial Dysfunction in Women Hypertension, October 1, 1996; 28(4): 576 - 582. [Abstract] [Full Text]
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G. Aliev, V. Ralevic, and G. Burnstock Depression of Endothelial Nitric Oxide Synthase but Increased Expression of Endothelin-1 Immunoreactivity in Rat Thoracic Aortic Endothelium Associated With Long-term, but Not Short-term, Sympathectomy Circ. Res., August 1, 1996; 79(2): 317 - 323. [Abstract] [Full Text]
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R. W. Jeremy, H. McCarron, and D. Sullivan Effects of Dietary L-Arginine on Atherosclerosis and Endothelium-Dependent Vasodilatationin the Hypercholesterolemic Rabbit: Response According to Treatment Duration, Anatomic Site, and Sex Circulation, August 1, 1996; 94(3): 498 - 506. [Abstract] [Full Text]
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H. Kato, J. Hou, A. V. Chobanian, and P. Brecher Effects of Angiotensin II Infusion and Inhibition of Nitric Oxide Synthase on the Rat Aorta Hypertension, August 1, 1996; 28(2): 153 - 158. [Abstract] [Full Text]
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W. S. Shin, Y.-H. Hong, H.-B. Peng, R. De Caterina, P. Libby, and J. K. Liao Nitric Oxide Attenuates Vascular Smooth Muscle Cell Activation by Interferon-[IMAGE] J. Biol. Chem., May 10, 1996; 271(19): 11317 - 11324. [Abstract] [Full Text] [PDF]
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D. M. Smalley, J. H.-C. Lin, M. L. Curtis, Y. Kobari, M. B. Stemerman, and K. A. Pritchard Jr Native LDL Increases Endothelial Cell Adhesiveness by Inducing Intercellular Adhesion Molecule–1 Arterioscler Thromb Vasc Biol, April 1, 1996; 16(4): 585 - 590. [Abstract] [Full Text]
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N. P. Lewis, P. S. Tsao, P. R. Rickenbacher, C. Xue, R. A. Johns, G. A. Haywood, H. von der Leyen, P. T. Trindade, J. P. Cooke, S. A. Hunt, et al. Induction of Nitric Oxide Synthase in the Human Cardiac Allograft Is Associated With Contractile Dysfunction of the Left Ventricle Circulation, February 15, 1996; 93(4): 720 - 729. [Abstract] [Full Text]
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R. C. Candipan, B.-y. Wang, R. Buitrago, P. S. Tsao, and J. P. Cooke Regression or Progression : Dependency on Vascular Nitric Oxide Arterioscler Thromb Vasc Biol, January 1, 1996; 16(1): 44 - 50. [Abstract] [Full Text]
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P. S. Tsao, N. P. Lewis, S. Alpert, and J. P. Cooke Exposure to Shear Stress Alters Endothelial Adhesiveness : Role of Nitric Oxide Circulation, December 15, 1995; 92(12): 3513 - 3519. [Abstract] [Full Text]
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T. Murohara, S. J. Parkinson, S. A. Waldman, and A. M. Lefer Inhibition of Nitric Oxide Biosynthesis Promotes P-selectin Expression in Platelets : Role of Protein Kinase C Arterioscler Thromb Vasc Biol, November 1, 1995; 15(11): 2068 - 2075. [Abstract] [Full Text]
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