© 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
This article has been cited by other articles:
 |
|
 |
|
  C. Ootaki, M. Yamashita, Y. Ootaki, K. Kamohara, S. Weber, R. S. Klatte, W. A. Smith, A. L. Massiello, S. N. Emancipator, L. A.R. Golding, et al. Reduced Pulsatility Induces Periarteritis in Kidney: Role of the Local Renin-Angiotensin System J. Thorac. Cardiovasc. Surg., July 1, 2008; 136(1): 150 - 158. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Lee, J.-C. Kim, Y. Li, M.-J. Son, and S.-H. Woo Fluid pressure modulates L-type Ca2+ channel via enhancement of Ca2+-induced Ca2+ release in rat ventricular myocytes Am J Physiol Cell Physiol, April 1, 2008; 294(4): C966 - C976. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Laughlin, S. C. Newcomer, and S. B. Bender Importance of hemodynamic forces as signals for exercise-induced changes in endothelial cell phenotype J Appl Physiol, March 1, 2008; 104(3): 588 - 600. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. C. W. Groenendijk, K. Van der Heiden, B. P. Hierck, and R. E. Poelmann The Role of Shear Stress on ET-1, KLF2, and NOS-3 Expression in the Developing Cardiovascular System of Chicken Embryos in a Venous Ligation Model Physiology, December 1, 2007; 22(6): 380 - 389. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-C. Tsai, H.-J. Hsieh, F. Liao, C.-W. Ni, Y.-J. Chao, C.-Y. Hsieh, and D. L. Wang Laminar flow attenuates interferon-induced inflammatory responses in endothelial cells Cardiovasc Res, June 1, 2007; 74(3): 497 - 505. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Saloner, G. Acevedo-Bolton, M. Wintermark, and J. H. Rapp MRI of Geometric and Compositional Features of Vulnerable Carotid Plaque Stroke, February 1, 2007; 38(2): 637 - 641. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yayama, H. Hiyoshi, D. Imazu, and H. Okamoto Angiotensin II Stimulates Endothelial NO Synthase Phosphorylation in Thoracic Aorta of Mice With Abdominal Aortic Banding Via Type 2 Receptor Hypertension, November 1, 2006; 48(5): 958 - 964. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Yin, Z. Wang, H. Zhu, R. Zhang, H. Wang, and X. Li Experimental Study of Effect of Fontan Circuit on Pulmonary Microcirculation Asian Cardiovasc Thorac Ann, June 1, 2006; 14(3): 183 - 188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Gambillara, C. Chambaz, G. Montorzi, S. Roy, N. Stergiopulos, and P. Silacci Plaque-prone hemodynamics impair endothelial function in pig carotid arteries Am J Physiol Heart Circ Physiol, June 1, 2006; 290(6): H2320 - H2328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. A. Arenas, Y. Xu, and S. T. Davidge Age-associated impairment in vasorelaxation to fluid shear stress in the female vasculature is improved by TNF-{alpha} antagonism Am J Physiol Heart Circ Physiol, March 1, 2006; 290(3): H1259 - H1263. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Vargas, J. M. Moreno, I. Rodriguez-Gomez, R. Wangensteen, A. Osuna, M. Alvarez-Guerra, and J. Garcia-Estan Vascular and renal function in experimental thyroid disorders Eur. J. Endocrinol., February 1, 2006; 154(2): 197 - 212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Reboul, S. Tanguy, A. Gibault, M. Dauzat, and P. Obert Chronic hypoxia exposure depresses aortic endothelium-dependent vasorelaxation in both sedentary and trained rats: involvement of L-arginine J Appl Physiol, September 1, 2005; 99(3): 1029 - 1035. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Alegria, J. Herrmann, D. R. Holmes Jr, A. Lerman, and C. S. Rihal Myocardial bridging Eur. Heart J., June 2, 2005; 26(12): 1159 - 1168. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Hiyoshi, K. Yayama, M. Takano, and H. Okamoto Angiotensin Type 2 Receptor-Mediated Phosphorylation of eNOS in the Aortas of Mice With 2-Kidney, 1-Clip Hypertension Hypertension, May 1, 2005; 45(5): 967 - 973. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R M McAllister, I Albarracin, E M Price, T K Smith, J R Turk, and K D Wyatt Thyroid status and nitric oxide in rat arterial vessels J. Endocrinol., April 1, 2005; 185(1): 111 - 119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Woodman, E. M. Price, and M. H. Laughlin Shear stress induces eNOS mRNA expression and improves endothelium-dependent dilation in senescent soleus muscle feed arteries J Appl Physiol, March 1, 2005; 98(3): 940 - 946. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Sokabe, K. Yamamoto, N. Ohura, H. Nakatsuka, K. Qin, S. Obi, A. Kamiya, and J. Ando Differential regulation of urokinase-type plasminogen activator expression by fluid shear stress in human coronary artery endothelial cells Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H2027 - H2034. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. L. Goodwin, L. P. Solomonson, and D. C. Eichler Argininosuccinate Synthase Expression Is Required to Maintain Nitric Oxide Production and Cell Viability in Aortic Endothelial Cells J. Biol. Chem., April 30, 2004; 279(18): 18353 - 18360. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Shimizu, S. Ito, Y. Kikuchi, M. Misaka, T. Hirayama, S. Ishimaru, and A. Yamashina Arterial conduit shear stress following bypass grafting for intermediate coronary artery stenosis: a comparative study with saphenous vein grafts Eur. J. Cardiothorac. Surg., April 1, 2004; 25(4): 578 - 584. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Loufrani, C. Dubroca, D. You, Z. Li, B. Levy, D. Paulin, and D. Henrion Absence of Dystrophin in Mice Reduces NO-Dependent Vascular Function and Vascular Density: Total Recovery After a Treatment with the Aminoglycoside Gentamicin Arterioscler. Thromb. Vasc. Biol., April 1, 2004; 24(4): 671 - 676. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Li, J. Zheng, I. M. Bird, and R. R. Magness Effects of Pulsatile Shear Stress on Nitric Oxide Production and Endothelial Cell Nitric Oxide Synthase Expression by Ovine Fetoplacental Artery Endothelial Cells Biol Reprod, September 1, 2003; 69(3): 1053 - 1059. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Hambrecht, V. Adams, S. Erbs, A. Linke, N. Krankel, Y. Shu, Y. Baither, S. Gielen, H. Thiele, J.F. Gummert, et al. Regular Physical Activity Improves Endothelial Function in Patients With Coronary Artery Disease by Increasing Phosphorylation of Endothelial Nitric Oxide Synthase Circulation, July 1, 2003; 107(25): 3152 - 3158. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Paddenberg, B. Ishaq, A. Goldenberg, P. Faulhammer, F. Rose, N. Weissmann, R. C. Braun-Dullaeus, and W. Kummer Essential role of complex II of the respiratory chain in hypoxia-induced ROS generation in the pulmonary vasculature Am J Physiol Lung Cell Mol Physiol, May 1, 2003; 284(5): L710 - L719. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. G. Lloyd, B. M. Prior, H. T. Yang, and R. L. Terjung Angiogenic growth factor expression in rat skeletal muscle in response to exercise training Am J Physiol Heart Circ Physiol, May 1, 2003; 284(5): H1668 - H1678. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wedgwood, C. J. Mitchell, J. R. Fineman, and S. M. Black Developmental differences in the shear stress-induced expression of endothelial NO synthase: changing role of AP-1 Am J Physiol Lung Cell Mol Physiol, April 1, 2003; 284(4): L650 - L662. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Paszkowiak and A. Dardik Arterial Wall Shear Stress: Observations from the Bench to the Bedside Vascular and Endovascular Surgery, January 1, 2003; 37(1): 47 - 57. [Abstract] [PDF]
|
|
|
|
|
|
C. R. Woodman, E. M. Price, and M. H. Laughlin Aging induces muscle-specific impairment of endothelium-dependent dilation in skeletal muscle feed arteries J Appl Physiol, November 1, 2002; 93(5): 1685 - 1690. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Irace, A. Gnasso, F. Cirillo, G. Leonardo, M. Ciamei, A. Crivaro, A. Renzulli, and M. Cotrufo Arterial Remodeling of the Common Carotid Artery After Aortic Valve Replacement in Patients With Aortic Stenosis Stroke, October 1, 2002; 33(10): 2446 - 2450. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Wang Role of iNOS and eNOS in modulating proximal tubule transport and acid-base balance Am J Physiol Renal Physiol, October 1, 2002; 283(4): F658 - F662. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kawano, T. Motoyama, H. Yasue, N. Hirai, H. M. Waly, K. Kugiyama, and H. Ogawa Endothelial function fluctuates with diurnal variation in the frequency of ischemic episodes in patients with variant angina J. Am. Coll. Cardiol., July 17, 2002; 40(2): 266 - 270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Joyce, T. M. Phernetton, and R. R. Magness Effect of Uterine Blood Flow Occlusion on Shear Stress-Mediated Nitric Oxide Production and Endothelial Nitric Oxide Synthase Expression During Ovine Pregnancy Biol Reprod, July 1, 2002; 67(1): 320 - 326. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. L. Boot, Jan. T. Groothuis, H. van Langen, and M. T. E. Hopman Shear stress levels in paralyzed legs of spinal cord-injured individuals with and without nerve degeneration J Appl Physiol, June 1, 2002; 92(6): 2335 - 2340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Dai, O. Tsukurov, M. Chen, J. P. Gertler, and R. D. Kamm Endothelial nitric oxide production during in vitro simulation of external limb compression Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2066 - H2075. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kihara, S. Biro, M. Imamura, S. Yoshifuku, K. Takasaki, Y. Ikeda, Y. Otuji, S. Minagoe, Y. Toyama, and C. Tei Repeated sauna treatment improves vascular endothelial and cardiac function in patients with chronic heart failure J. Am. Coll. Cardiol., March 6, 2002; 39(5): 754 - 759. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-E. Chen, K. Liu, W.-N. Qi, E. Joneschild, X. Tan, A. V. Seaber, J. S. Stamler, and J. R. Urbaniak Role of nitric oxide in vasodilation in upstream muscle during intermittent pneumatic compression J Appl Physiol, February 1, 2002; 92(2): 559 - 566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. T. Yang, J. Ren, M. H. Laughlin, and R. L. Terjung Prior exercise training produces NO-dependent increases in collateral blood flow after acute arterial occlusion Am J Physiol Heart Circ Physiol, January 1, 2002; 282(1): H301 - H310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Joyce, T. M. Phernetton, C. E. Shaw, M. L. Modrick, and R. R. Magness Endothelial vasodilator production by uterine and systemic arteries. IX. eNOS gradients in cycling and pregnant ewes Am J Physiol Heart Circ Physiol, January 1, 2002; 282(1): H342 - H348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Gaenzer, G. Neumayr, P. Marschang, W. Sturm, R. Kirchmair, and J. R. Patsch Flow-mediated vasodilation of the femoral and brachial artery induced by exercise in healthy nonsmoking and smoking men J. Am. Coll. Cardiol., November 1, 2001; 38(5): 1313 - 1319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Song, A. B. Al-Mehdi, and A. B. Fisher An immediate endothelial cell signaling response to lung ischemia Am J Physiol Lung Cell Mol Physiol, October 1, 2001; 281(4): L993 - L1000. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Woodman, W. G. Schrage, J. W. E. Rush, C. A. Ray, E. M. Price, E. M. Hasser, and M. H. Laughlin Hindlimb unweighting decreases endothelium-dependent dilation and eNOS expression in soleus not gastrocnemius J Appl Physiol, September 1, 2001; 91(3): 1091 - 1098. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Tuttle, R. D. Nachreiner, A. S. Bhuller, K. W. Condict, B. A. Connors, B. P. Herring, M. C. Dalsing, and J. L. Unthank Shear level influences resistance artery remodeling: wall dimensions, cell density, and eNOS expression Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1380 - H1389. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wedgwood, J. M. Bekker, and S. M. Black Shear stress regulation of endothelial NOS in fetal pulmonary arterial endothelial cells involves PKC Am J Physiol Lung Cell Mol Physiol, August 1, 2001; 281(2): L490 - L498. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Nakano, R. Tominaga, S. Morita, M. Masuda, I. Nagano, K.-i. Imasaka, and H. Yasui Impacts of pulsatile systemic circulation on endothelium-derived nitric oxide release in anesthetized dogs Ann. Thorac. Surg., July 1, 2001; 72(1): 156 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kurotobi, T. Sano, S. Kogaki, T. Matsushita, T. Miwatani, M. Takeuchi, H. Matsuda, and S. Okada Bidirectional cavopulmonary shunt with right ventricular outflow patency: The impact of pulsatility on pulmonary endothelial function J. Thorac. Cardiovasc. Surg., June 1, 2001; 121(6): 1161 - 1168. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. R. Johnson, J. W. E. Rush, J. R. Turk, E. M. Price, and M. H. Laughlin Short-term exercise training increases ACh-induced relaxation and eNOS protein in porcine pulmonary arteries J Appl Physiol, March 1, 2001; 90(3): 1102 - 1110. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Govers and T. J. Rabelink Cellular regulation of endothelial nitric oxide synthase Am J Physiol Renal Physiol, February 1, 2001; 280(2): F193 - F206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Gielen, G. Schuler, and R. Hambrecht Exercise Training in Coronary Artery Disease and Coronary Vasomotion Circulation, January 2, 2001; 103 (1): e1 - e6. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Gosgnach, D. Messika-Zeitoun, W. Gonzalez, M. Philipe, and J.-B. Michel Shear stress induces iNOS expression in cultured smooth muscle cells: role of oxidative stress Am J Physiol Cell Physiol, December 1, 2000; 279(6): C1880 - C1888. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Urbich, D. H. Walter, A. M. Zeiher, and S. Dimmeler Laminar Shear Stress Upregulates Integrin Expression : Role in Endothelial Cell Adhesion and Apoptosis Circ. Res., October 13, 2000; 87(8): 683 - 689. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Jen, S.-J. Jhiang, and H.-I. Chen Cellular Responses to Mechanical Stress: Invited Review: Effects of flow on vascular endothelial intracellular calcium signaling of rat aortas ex vivo J Appl Physiol, October 1, 2000; 89(4): 1657 - 1662. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. T. Yang, M. H. Laughlin, and R. L. Terjung Prior exercise training increases collateral-dependent blood flow in rats after acute femoral artery occlusion Am J Physiol Heart Circ Physiol, October 1, 2000; 279(4): H1890 - H1897. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-m. Gan, L. Selin-Sjogren, R. Doroudi, and S. Jern Temporal regulation of endothelial ET-1 and eNOS expression in intact human conduit vessels exposed to different intraluminal pressure levels at physiological shear stress Cardiovasc Res, October 1, 2000; 48(1): 168 - 177. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Lin, P.-P. Hsu, B. P. Chen, S. Yuan, S. Usami, J. Y.-J. Shyy, Y.-S. Li, and S. Chien Molecular mechanism of endothelial growth arrest by laminar shear stress PNAS, July 30, 2000; (2000) 170282597. [Abstract] [Full Text]
|
|
|
|
|
|
M. J VanWijk, K. Kublickiene, K. Boer, and E. VanBavel Vascular function in preeclampsia Cardiovasc Res, July 1, 2000; 47(1): 38 - 48. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. S. Wittstein, W. Qiu, R. C. Ziegelstein, Q. Hu, and D. A. Kass Opposite Effects of Pressurized Steady Versus Pulsatile Perfusion on Vascular Endothelial Cell Cytosolic pH : Role of Tyrosine Kinase and Mitogen-Activated Protein Kinase Signaling Circ. Res., June 23, 2000; 86(12): 1230 - 1236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. R. Johnson and M. H. Laughlin Chronic exercise training does not alter pulmonary vasorelaxation in normal pigs J Appl Physiol, June 1, 2000; 88(6): 2008 - 2014. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Gnasso, C. Motti, C. Irace, C. Carallo, L. Liberatoscioli, S. Bernardini, R. Massoud, P. L. Mattioli, G. Federici, and C. Cortese Genetic Variation in Human Stromelysin Gene Promoter and Common Carotid Geometry in Healthy Male Subjects Arterioscler. Thromb. Vasc. Biol., June 1, 2000; 20(6): 1600 - 1605. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
< |