Arteriosclerosis, Thrombosis, and Vascular Biology. 1996;16:1256-1262
© 1996 American Heart Association, Inc.
Articles |
Role of NO in Flow-Induced Remodeling of the Rabbit Common Carotid Artery
the Institut National de la Sante et de la Recherche Medicale (F.T., B.E., D.H., A.T.), the Department of Pathology (M.W.), Institut Federatif de Recherche "Circulation Lariboisiere," Hopital Lariboisiere, Paris, France, and the Department of Pathology (S.G.), University of Chicago, Chicago, Ill.
Correspondence to Alain Tedgui, PhD, INSERM Unite 141, 41 boulevard de la Chapelle, 75475 Paris, France.
Flow-induced changes in vessel caliber tend to restore baseline wall shear stress (WSS) and have been reported to be endothelium-dependent. To investigate the role of endothelium-derived nitric oxide (NO) in the adaptive increase in artery diameter in response to a chronic increase in blood flow, an arteriovenous fistula was constructed between the left common carotid artery (CCA) and the external jugular vein in 22 New Zealand White rabbits, and NO synthesis was inhibited in 14 animals by long-term administration of NG-nitro-L-arginine-methyl ester (L-NAME) in drinking water given for 4 weeks. The remaining 8 animals served as controls. Mean arterial blood pressure was not significantly altered by L-NAME treatment (91±2 in control versus 98±3 mm Hg in L-NAME–treated rabbits). Blood flow significantly increased in the left CCA in both groups but was lower in L-NAME–treated than control animals (106.1±10.7 versus 196.2±32.3 mL/min, P<.003). The diameter of the flow-loaded left CCA also increased significantly in both groups compared with the right CCA (2.15±0.12 and 2.54±0.1 mm, respectively, P<.02), but the increase was less in the L-NAME–treated than the control group (3.24±0.09 and 4.64±0.17 mm, respectively, P<.0001). The diameter of the anastomosed veins was also increased but to a much lesser degree in L-NAME–treated animals than in controls (4.14±0.29 versus 7.94±0.51 mm, P<.0001). As a result of artery enlargement, WSS was normalized in the flow-loaded left CCA of the control group (8.87±0.77 dynes/cm2) regardless of blood flow values. In L-NAME–treated animals, however, WSS was only partially regulated, the mean value being significantly increased (18.7±2.2 dynes/cm2, P<.006). Moreover, a highly significant positive correlation between WSS and blood flow was obtained in L-NAME–treated animals (r=.84, P<.0001). We also found remodeling of the artery wall, with a larger increase in the medial cross-sectional area associated with an increased number of smooth muscle cells, in the control group compared with the L-NAME–treated group (0.75±0.09 versus 0.49±0.04 mm2 and 4504±722 versus 2717±282 cells/mm2, P<.03). We conclude that NO plays a role in the increase of vessel caliber in response to chronic increase in blood flow. As yet unidentified additional metabolic processes appear to be necessary for a complete regulatory response.
Key Words: endothelium • wall shear stress • vascular enlargement • hyperplasia • smooth muscle cell
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R. D. Rudic, M. Bucci, D. Fulton, S. S. Segal, and W. C. Sessa Temporal Events Underlying Arterial Remodeling After Chronic Flow Reduction in Mice : Correlation of Structural Changes With a Deficit in Basal Nitric Oxide Synthesis Circ. Res., June 9, 2000; 86(11): 1160 - 1166. [Abstract] [Full Text] [PDF]
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 K. J. Harmon, L. L. Couper, and V. Lindner Strain-Dependent Vascular Remodeling Phenotypes in Inbred Mice Am. J. Pathol., May 1, 2000; 156(5): 1741 - 1748. [Abstract] [Full Text] [PDF]
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S. P. Schwarzacher, N. G. Uren, M. R. Ward, A. Schwarzkopf, N. Giannetti, S. Hunt, P. J. Fitzgerald, S. N. Oesterle, and A. C. Yeung Determinants of Coronary Remodeling in Transplant Coronary Disease : A Simultaneous Intravascular Ultrasound and Doppler Flow Study Circulation, March 28, 2000; 101(12): 1384 - 1389. [Abstract] [Full Text] [PDF]
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P. M. H. Schiffers, D. Henrion, C. M. Boulanger, E. Colucci-Guyon, F. Langa-Vuves, H. van Essen, G. E. Fazzi, B. I. Levy, and J. G. R. De Mey Altered Flow-Induced Arterial Remodeling in Vimentin-Deficient Mice Arterioscler Thromb Vasc Biol, March 1, 2000; 20(3): 611 - 616. [Abstract] [Full Text] [PDF]
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G. Pasterkamp, D. P.V de Kleijn, and C. Borst Arterial remodeling in atherosclerosis, restenosis and after alteration of blood flow: potential mechanisms and clinical implications Cardiovasc Res, March 1, 2000; 45(4): 843 - 852. [Abstract] [Full Text] [PDF]
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G. Marano, S. Palazzesi, A. Vergari, and A. U. Ferrari Protection by Shear Stress From Collar-Induced Intimal Thickening : Role of Nitric Oxide Arterioscler Thromb Vasc Biol, November 1, 1999; 19(11): 2609 - 2614. [Abstract] [Full Text] [PDF]
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H. Masuda, Y.-J. Zhuang, T. M. Singh, K. Kawamura, M. Murakami, C. K. Zarins, and S. Glagov Adaptive Remodeling of Internal Elastic Lamina and Endothelial Lining During Flow-Induced Arterial Enlargement Arterioscler Thromb Vasc Biol, October 1, 1999; 19(10): 2298 - 2307. [Abstract] [Full Text] [PDF]
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A. Lafont, E. Durand, J. L. Samuel, B. Besse, F. Addad, B. I. Levy, M. Desnos, C. Guerot, and C. M. Boulanger Endothelial Dysfunction and Collagen Accumulation : Two Independent Factors for Restenosis and Constrictive Remodeling After Experimental Angioplasty Circulation, September 7, 1999; 100(10): 1109 - 1115. [Abstract] [Full Text] [PDF]
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A. Papapetropoulos, R. D. Rudic, and W. C Sessa Molecular control of nitric oxide synthases in the cardiovascular system Cardiovasc Res, August 15, 1999; 43(3): 509 - 520. [Abstract] [Full Text] [PDF]
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F. R. L. Crijns, B. H. R. Wolffenbuttel, J. G. R. de Mey, and H. A. J. S. Boudier Mechanical properties of mesenteric arteries in diabetic rats: consequences of outward remodeling Am J Physiol Heart Circ Physiol, May 1, 1999; 276(5): H1672 - H1677. [Abstract] [Full Text] [PDF]
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C. Brown, X. Pan, and A. Hassid Nitric Oxide and C-Type Atrial Natriuretic Peptide Stimulate Primary Aortic Smooth Muscle Cell Migration via a cGMP-Dependent Mechanism : Relationship to Microfilament Dissociation and Altered Cell Morphology Circ. Res., April 2, 1999; 84(6): 655 - 667. [Abstract] [Full Text] [PDF]
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W. J. Calvo, G. Hajduczok, J. A. Russell, and S. L. Diamond Inhibition of Nitric Oxide but Not Prostacyclin Prevents Poststenotic Dilatation in Rabbit Femoral Artery Circulation, March 2, 1999; 99(8): 1069 - 1076. [Abstract] [Full Text] [PDF]
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 T. Le Tourneau, E. Van Belle, D. Corseaux, B. Vallet, G. Lebuffe, B. Dupuis, J.-M. Lablanche, E. McFadden, C. Bauters, and M. E. Bertrand Role of nitric oxide in restenosis after experimental balloon angioplasty in the hypercholesterolemic rabbit: effects on neointimal hyperplasia and vascular remodeling J. Am. Coll. Cardiol., March 1, 1999; 33(3): 876 - 882. [Abstract] [Full Text] [PDF]
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S. R. Bryant, R. J. Bjercke, D. A. Erichsen, A. Rege, and V. Lindner Vascular Remodeling in Response to Altered Blood Flow Is Mediated by Fibroblast Growth Factor-2 Circ. Res., February 19, 1999; 84(3): 323 - 328. [Abstract] [Full Text] [PDF]
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I. J. Kullo, R. D. Simari, and R. S. Schwartz Vascular Gene Transfer : From Bench to Bedside Arterioscler Thromb Vasc Biol, February 1, 1999; 19(2): 196 - 207. [Full Text] [PDF]
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 E. V. Vitvitsky, J. P. Griffin, M. H. Collins, T. L. Spray, and J. W. Gaynor Increased pulmonary blood flow produces endothelial cell dysfunction in neonatal swine Ann. Thorac. Surg., October 1, 1998; 66(4): 1372 - 1377. [Abstract] [Full Text] [PDF]
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S. Lehoux and A. Tedgui Signal Transduction of Mechanical Stresses in the Vascular Wall Hypertension, August 1, 1998; 32(2): 338 - 345. [Abstract] [Full Text] [PDF]
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E. Van Belle, C. Bauters, T. Asahara, and J. M. Isner Endothelial regrowth after arterial injury: from vascular repair to therapeutics Cardiovasc Res, April 1, 1998; 38(1): 54 - 68. [Full Text] [PDF]
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M. Papadaki, R. G. Tilton, S. G. Eskin, and L. V. McIntire Nitric oxide production by cultured human aortic smooth muscle cells: stimulation by fluid flow Am J Physiol Heart Circ Physiol, February 1, 1998; 274(2): H616 - H626. [Abstract] [Full Text] [PDF]
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J. K. Miyashiro, V. Poppa, and B. C. Berk Flow-Induced Vascular Remodeling in the Rat Carotid Artery Diminishes With Age Circ. Res., September 19, 1997; 81(3): 311 - 319. [Abstract] [Full Text]
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