© 1995 American Heart Association, Inc.
Articles |
Nitric Oxide Synthesis by Cultured Endothelial Cells Is Modulated by Flow Conditions
From the Mario Negri Institute for Pharmacological Research (M.N., M.M., R.D., S.A., M.F., M.T., S.O., G.R., A.R.) and the Division of Nephrology (G.R.), Ospedali Riuniti di Bergamo (Italy).
Correspondence to Marina Noris, Mario Negri Institute for Pharmacological Research, Via Gavazzeni 11, 24125 Bergamo, Italy.
Abstract In the present study, we examined the hypothesis that dynamic characteristics of flow modulate the production of vasoactive mediators, namely nitric oxide (NO) and endothelin-1 (ET-1), by human umbilical vein endothelial cells (HUVECs). Cells were exposed for 6 hours in a cone-and-plate apparatus to different types of flow: steady laminar, with shear stresses of 2, 8, and 12 dyne/cm2; pulsatile laminar, with shear stress from 8.2 to 16.6 dyne/cm2 and a frequency of 2 Hz; periodic laminar, with square wave cycles of 15 minutes and shear stress from 2 to 8 dyne/cm2; and turbulent, with shear stress of 8 dyne/cm2 on average. A second culture dish was kept in a normal incubator as a static control for each experiment. Laminar flow induced synthesis of NO by HUVECs that was dependent on shear-stress magnitude. Laminar shear stress at 8 dyne/cm2 also upregulated the level of NO synthase mRNA. As observed with steady laminar flow, pulsatile flow also induced an increase in NO release by endothelial cells. When HUVECs were subjected to step-change increases of laminar shear, a further increase of NO synthesis was observed, compared with steady laminar shear of the same magnitude. Turbulent flow did not upregulate NO synthase mRNA or increase NO release. Both laminar and turbulent shear stress reduced, although not significantly, ET-1 mRNA and ET-1 production compared with the static condition. These results indicate that local blood flow conditions modulate the production of vasoactive substances by endothelial cells. This may affect vascular cell functions such as nonthrombogenicity, regulation of blood flow, and vascular tone.
Key Words: atherosclerosis • endothelium-derived relaxing factor • endothelin • gene expression • shear stress
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S. Dimmeler, C. Hermann, J. Galle, and A. M. Zeiher Upregulation of Superoxide Dismutase and Nitric Oxide Synthase Mediates the Apoptosis-Suppressive Effects of Shear Stress on Endothelial Cells Arterioscler Thromb Vasc Biol, March 1, 1999; 19(3): 656 - 664. [Abstract] [Full Text] [PDF]
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C. R. Woodman, J. M. Muller, J. W. E. Rush, M. H. Laughlin, and E. M. Price Flow regulation of ecNOS and Cu/Zn SOD mRNA expression in porcine coronary arterioles Am J Physiol Heart Circ Physiol, March 1, 1999; 276(3): H1058 - H1063. [Abstract] [Full Text] [PDF]
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X. Q. Wang and N. D. Vaziri Erythropoietin Depresses Nitric Oxide Synthase Expression by Human Endothelial Cells Hypertension, March 1, 1999; 33(3): 894 - 899. [Abstract] [Full Text] [PDF]
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M. B. Patel, I. V. Kaplan, R. N. Patni, D. Levy, J. A. Strom, J. Shirani, and T. H. LeJemtel Sustained Improvement in Flow-Mediated Vasodilation After Short-Term Administration of Dobutamine in Patients With Severe Congestive Heart Failure Circulation, January 12, 1999; 99(1): 60 - 64. [Abstract] [Full Text] [PDF]
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R. Hambrecht, E. Fiehn, C. Weigl, S. Gielen, C. Hamann, R. Kaiser, J. Yu, V. Adams, J. Niebauer, and G. Schuler Regular Physical Exercise Corrects Endothelial Dysfunction and Improves Exercise Capacity in Patients With Chronic Heart Failure Circulation, December 15, 1998; 98(24): 2709 - 2715. [Abstract] [Full Text] [PDF]
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K. Okahara, B. Sun, and J.-i. Kambayashi Upregulation of Prostacyclin Synthesis–Related Gene Expression by Shear Stress in Vascular Endothelial Cells Arterioscler Thromb Vasc Biol, December 1, 1998; 18(12): 1922 - 1926. [Abstract] [Full Text] [PDF]
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S. M. Black, J. R. Fineman, R. H. Steinhorn, J. Bristow, and S. J. Soifer Increased endothelial NOS in lambs with increased pulmonary blood flow and pulmonary hypertension Am J Physiol Heart Circ Physiol, November 1, 1998; 275(5): H1643 - H1651. [Abstract] [Full Text] [PDF]
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T. Minamino, M. Kitakaze, S. Sanada, H. Asanuama, T. Kurotobi, Y. Koretsune, M. Fukunami, T. Kuzuya, N. Hoki, and M. Hori Increased Expression of P-Selectin on Platelets Is a Risk Factor for Silent Cerebral Infarction in Patients With Atrial Fibrillation : Role of Nitric Oxide Circulation, October 27, 1998; 98(17): 1721 - 1727. [Abstract] [Full Text] [PDF]
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Y. Ding and N. D. Vaziri Calcium Channel Blockade Enhances Nitric Oxide Synthase Expression by Cultured Endothelial Cells Hypertension, October 1, 1998; 32(4): 718 - 723. [Abstract] [Full Text] [PDF]
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Z. Ni, X. Q. Wang, and N. D. Vaziri Nitric Oxide Metabolism in Erythropoietin-Induced Hypertension : Effect of Calcium Channel Blockade Hypertension, October 1, 1998; 32(4): 724 - 729. [Abstract] [Full Text] [PDF]
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S. Dimmeler, B. Assmus, C. Hermann, J. Haendeler, and A. M. Zeiher Fluid Shear Stress Stimulates Phosphorylation of Akt in Human Endothelial Cells : Involvement in Suppression of Apoptosis Circ. Res., August 10, 1998; 83(3): 334 - 341. [Abstract] [Full Text] [PDF]
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A. Zanchi, N. Stergiopulos, H. R. Brunner, and D. Hayoz Differences in the Mechanical Properties of the Rat Carotid Artery In Vivo, In Situ, and In Vitro Hypertension, July 1, 1998; 32(1): 180 - 185. [Abstract] [Full Text] [PDF]
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N. Thorin-Trescases, J. A. Bevan, and W. J. Pearce High Levels of Myogenic Tone Antagonize the Dilator Response to Flow of Small Rabbit Cerebral Arteries • Editorial Comment Stroke, June 1, 1998; 29(6): 1194 - 1201. [Abstract] [Full Text] [PDF]
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N. D. Vaziri, Z. Ni, X. Q. Wang, F. Oveisi, and X. J. Zhou Downregulation of nitric oxide synthase in chronic renal insufficiency: role of excess PTH Am J Physiol Renal Physiol, April 1, 1998; 274(4): F642 - F649. [Abstract] [Full Text] [PDF]
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H. Watanabe, R. Takahashi, X.-x. Zhang, Y. Goto, H. Hayashi, J. Ando, M. Isshiki, M. Seto, H. Hidaka, I. Niki, et al. An essential role of myosin light-chain kinase in the regulation of agonist- and fluid flow-stimulated Ca2+ influx in endothelial cells FASEB J, March 1, 1998; 12(3): 341 - 348. [Abstract] [Full Text]
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 K. Wada, Y. Kamisaki, T. Ohkura, G. Kanda, K. Nakamoto, Y. Kishimoto, K. Ashida, and T. Itoh Direct measurement of nitric oxide release in gastric mucosa during ischemia-reperfusion in rats Am J Physiol Gastrointest Liver Physiol, March 1, 1998; 274(3): G465 - G471. [Abstract] [Full Text] [PDF]
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L. J. Andries, D. L. Brutsaert, and S. U. Sys Nonuniformity of Endothelial Constitutive Nitric Oxide Synthase Distribution in Cardiac Endothelium Circ. Res., February 9, 1998; 82(2): 195 - 203. [Abstract] [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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S. Dimmeler, V. Rippmann, U. Weiland, J. Haendeler, and A. M. Zeiher Angiotensin II Induces Apoptosis of Human Endothelial Cells : Protective Effect of Nitric Oxide Circ. Res., December 19, 1997; 81(6): 970 - 976. [Abstract] [Full Text]
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C. Hermann, A. M. Zeiher, and S. Dimmeler Shear Stress Inhibits H2O2-Induced Apoptosis of Human Endothelial Cells by Modulation of the Glutathione Redox Cycle and Nitric Oxide Synthase Arterioscler Thromb Vasc Biol, December 1, 1997; 17(12): 3588 - 3592. [Abstract] [Full Text]
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M. van Bilsen Signal transduction revisited: recent developments in angiotensin II signaling in the cardiovascular system Cardiovasc Res, December 1, 1997; 36(3): 310 - 322. [Full Text] [PDF]
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Z.-G. Zhu, H.-H. Li, and B.-R. Zhang Expression of Endothelin-1 and Constitutional Nitric Oxide Synthase Messenger RNA in Saphenous Vein Endothelial Cells Exposed to Arterial Flow Shear Stress Ann. Thorac. Surg., November 1, 1997; 64(5): 1333 - 1338. [Abstract] [Full Text]
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T. Minamino, M. Kitakaze, H. Sato, H. Asanuma, H. Funaya, Y. Koretsune, and M. Hori Plasma Levels of Nitrite/Nitrate and Platelet cGMP Levels Are Decreased in Patients With Atrial Fibrillation Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 3191 - 3195. [Abstract] [Full Text]
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J. Wang, G.-H. Yi, M. Knecht, B.-l. Cai, S. Poposkis, M. Packer, and D. Burkhoff Physical Training Alters the Pathogenesis of Pacing-Induced Heart Failure Through Endothelium-Mediated Mechanisms in Awake Dogs Circulation, October 21, 1997; 96(8): 2683 - 2692. [Abstract] [Full Text]
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 R. A. Ahokas, S. A. Friedman, and B. M. Sibai Effect of Indomethacin and N{omega}-Nitro-L-Arginine Methyl Ester on the Pressure/Flow Relation in Isolated Perfused Hindlimbs From Pregnant and Nonpregnant Rats Reproductive Sciences, September 1, 1997; 4(5): 229 - 235. [Abstract] [PDF]
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 M. Galbusera, C. Zoja, R. Donadelli, S. Paris, M. Morigi, A. Benigni, M. Figliuzzi, G. Remuzzi, and A. Remuzzi Fluid Shear Stress Modulates von Willebrand Factor Release From Human Vascular Endothelium Blood, August 15, 1997; 90(4): 1558 - 1564. [Abstract] [Full Text] [PDF]
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J. H. Chammas, David. A. Rickaby, M. Guarin, J. H. Linehan, C. C. Hanger, and C. A. Dawson Flow-induced vasodilation in the ferret lung J Appl Physiol, August 1, 1997; 83(2): 495 - 502. [Abstract] [Full Text] [PDF]
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