© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Tetrahydrobiopterin and endothelial nitric oxide synthase activity
aCardiology, University Hospital and Cardiovascular Research, Institute of Physiology, Zürich, Switzerland
bIRCCS Neuromed, Pozzilli (IS), Italy
* Corresponding author. Tel.: +41-1-255-2121; fax: +41-1-255-4251 100771.1237@compuserve.com
Received 30 December 1998; accepted 18 March 1999
| The first 150 words of the full text of this article appear below. |
 |
1 Introduction |
|---|
Nitric oxide (NO) plays a crucial role in the regulation of vascular tone and maintenance of vascular integrity [1–3]. Indeed, nitric oxide reduces vascular tone, inhibits leucocytes adhesion to the endothelium, platelet-vessel wall interaction, as well as vascular smooth muscle cell proliferation and migration. Accordingly, major risk factors for atherosclerotic vascular disease such as hypercholesterolemia, diabetes, hypertension and smoking, have been associated with impaired nitric oxide activity [4–11].
In vivo the activity of the L-arginine-NO pathway is a balance between the synthesis and breakdown of NO. Although, there are several reasons to believe that NO synthesis could be impaired [12–14], reduced NO activity could be caused by enhanced catabolism. Indeed, the in vivo half-life of NO is determined mainly by its reaction with oxyhemoglobin and superoxide anion [15]. Superoxide (O2–) may rapidly react with NO to produce peroxynitrite (OONO–; [16]). This reaction
|
2 Effects of tetrahydrobiopterin on NOS activity |
|---|
|
3 Conclusions |
|---|
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Stangl and V. Stangl The ubiquitin proteasome pathway and endothelial (dys)function Cardiovasc Res, October 13, 2009; (2009) cvp315v2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Potenza, F. Addabbo, and M. Montagnani Vascular actions of insulin with implications for endothelial dysfunction Am J Physiol Endocrinol Metab, September 1, 2009; 297(3): E568 - E577. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Sindler, M. D. Delp, R. Reyes, G. Wu, and J. M. Muller-Delp Effects of ageing and exercise training on eNOS uncoupling in skeletal muscle resistance arterioles J. Physiol., August 1, 2009; 587(15): 3885 - 3897. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Tie, X.-J. Li, X. Wang, K. M. Channon, and A. F. Chen Endothelium-specific GTP cyclohydrolase I overexpression accelerates refractory wound healing by suppressing oxidative stress in diabetes Am J Physiol Endocrinol Metab, June 1, 2009; 296(6): E1423 - E1429. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Sugiyama, B. D. Levy, and T. Michel Tetrahydrobiopterin Recycling, a Key Determinant of Endothelial Nitric-oxide Synthase-dependent Signaling Pathways in Cultured Vascular Endothelial Cells J. Biol. Chem., May 8, 2009; 284(19): 12691 - 12700. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. de Waard, J. van der Velden, N. M. Boontje, D. H. W. Dekkers, R. van Haperen, D. W. D. Kuster, J. M. J. Lamers, R. de Crom, and D. J. Duncker Detrimental effect of combined exercise training and eNOS overexpression on cardiac function after myocardial infarction Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1513 - H1523. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Bashan, J. Kovsan, I. Kachko, H. Ovadia, and A. Rudich Positive and Negative Regulation of Insulin Signaling by Reactive Oxygen and Nitrogen Species Physiol Rev, January 1, 2009; 89(1): 27 - 71. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Wang, J. Xu, P. Song, Y. Wu, J. Zhang, H. Chul Choi, and M.-H. Zou Acute Inhibition of Guanosine Triphosphate Cyclohydrolase 1 Uncouples Endothelial Nitric Oxide Synthase and Elevates Blood Pressure Hypertension, September 1, 2008; 52(3): 484 - 490. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F Cosentino, D Hurlimann, C Delli Gatti, R Chenevard, N Blau, N J Alp, K M Channon, M Eto, P Lerch, F Enseleit, et al. Chronic treatment with tetrahydrobiopterin reverses endothelial dysfunction and oxidative stress in hypercholesterolaemia Heart, April 1, 2008; 94(4): 487 - 492. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Jackson, D. Pye, and J. Palomero The production of reactive oxygen and nitrogen species by skeletal muscle J Appl Physiol, April 1, 2007; 102(4): 1664 - 1670. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-M. Stevens, S. Fortier, M.-C. Aubin, I. El-Hamamsy, S. Maltais, M. Carrier, and L. P. Perrault Effect of tetrahydrobiopterin on selective endothelial dysfunction of epicardial porcine coronary arteries induced by cardiopulmonary bypass. Eur. J. Cardiothorac. Surg., September 1, 2006; 30(3): 464 - 471. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J Jackson Reactive oxygen species and redox-regulation of skeletal muscle adaptations to exercise Phil Trans R Soc B, December 29, 2005; 360(1464): 2285 - 2291. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. D. Loomis, J. C. Sullivan, D. A. Osmond, D. M. Pollock, and J. S. Pollock Endothelin Mediates Superoxide Production and Vasoconstriction through Activation of NADPH Oxidase and Uncoupled Nitric-Oxide Synthase in the Rat Aorta J. Pharmacol. Exp. Ther., December 1, 2005; 315(3): 1058 - 1064. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Eskurza, L. A Myerburgh, Z. D Kahn, and D. R Seals Tetrahydrobiopterin augments endothelium-dependent dilatation in sedentary but not in habitually exercising older adults J. Physiol., November 1, 2005; 568(3): 1057 - 1065. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Mittermayer, J. Pleiner, G. Schaller, S. Zorn, K. Namiranian, S. Kapiotis, G. Bartel, M. Wolfrum, M. Brugel, J. Thiery, et al. Tetrahydrobiopterin corrects Escherichia coli endotoxin-induced endothelial dysfunction Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1752 - H1757. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Molnar, S. Yu, N. Mzhavia, C. Pau, I. Chereshnev, and H. M. Dansky Diabetes Induces Endothelial Dysfunction but Does Not Increase Neointimal Formation in High-Fat Diet Fed C57BL/6J Mice Circ. Res., June 10, 2005; 96(11): 1178 - 1184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Lee, J.-m. Kim, H. J. Kim, I. Lee, and N. Chang Folic Acid Supplementation Can Reduce the Endothelial Damage in Rat Brain Microvasculature Due to Hyperhomocysteinemia J. Nutr., March 1, 2005; 135(3): 544 - 548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Bauersachs and A. Schafer Tetrahydrobiopterin and eNOS dimer/monomer ratio-a clue to eNOS uncoupling in diabetes? Cardiovasc Res, March 1, 2005; 65(4): 768 - 769. [Full Text] [PDF]
|
|
|
|
|
|
S. Cai, J. Khoo, and K. M. Channon Augmented BH4 by gene transfer restores nitric oxide synthase function in hyperglycemic human endothelial cells Cardiovasc Res, March 1, 2005; 65(4): 823 - 831. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mochizuki, P. Sipkema, M. Goto, O. Hiramatsu, H. Nakamoto, E. Toyota, T. Kajita, F. Shigeto, T. Yada, Y. Ogasawara, et al. Exogenous NO suppresses flow-induced endothelium-derived NO production because of depletion of tetrahydrobiopterin Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H553 - H558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Blackwell, J. P. Sorenson, D. M. Richardson, L. A. Smith, O. Suda, K. Nath, and Z. S. Katusic Mechanisms of aging-induced impairment of endothelium-dependent relaxation: role of tetrahydrobiopterin Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2448 - H2453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. W. Powers, R. E. Gandley, D. L. Lykins, and J. M. Roberts Moderate Hyperhomocysteinemia Decreases Endothelial-Dependent Vasorelaxation in Pregnant But Not Nonpregnant Mice Hypertension, September 1, 2004; 44(3): 327 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. d. C. P. Franco, Z. B. Fortes, E. H. Akamine, E. M. Kawamoto, C. Scavone, L. R. G. de Britto, M. N. Muscara, S. A. Teixeira, R. C. A. Tostes, M. H. C. Carvalho, et al. Tetrahydrobiopterin improves endothelial dysfunction and vascular oxidative stress in microvessels of intrauterine undernourished rats J. Physiol., July 1, 2004; 558(1): 239 - 248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kawashima and M. Yokoyama Dysfunction of Endothelial Nitric Oxide Synthase and Atherosclerosis Arterioscler Thromb Vasc Biol, June 1, 2004; 24(6): 998 - 1005. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Saraswathi, G. Wu, M. Toborek, and B. Hennig Linoleic acid-induced endothelial activation: role of calcium and peroxynitrite signaling J. Lipid Res., May 1, 2004; 45(5): 794 - 804. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-S. Zheng, X.-Q. Yang, K. J. Lookingland, G. D. Fink, C. Hesslinger, G. Kapatos, I. Kovesdi, and A. F. Chen Gene Transfer of Human Guanosine 5'-Triphosphate Cyclohydrolase I Restores Vascular Tetrahydrobiopterin Level and Endothelial Function in Low Renin Hypertension Circulation, September 9, 2003; 108(10): 1238 - 1245. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hattori, N. Nakanishi, K. Akimoto, M. Yoshida, and K. Kasai HMG-CoA Reductase Inhibitor Increases GTP Cyclohydrolase I mRNA and Tetrahydrobiopterin in Vascular Endothelial Cells Arterioscler Thromb Vasc Biol, February 1, 2003; 23(2): 176 - 182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Yang, N. Levens, J. N. Zhang, P. M. Vanhoutte, and M. Feletou Specific Potentiation of Endothelium-Dependent Contractions in SHR by Tetrahydrobiopterin Hypertension, January 1, 2003; 41(1): 136 - 142. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Cai, N. J Alp, D. McDonald, I. Smith, J. Kay, L. Canevari, S. Heales, and K. M Channon GTP cyclohydrolase I gene transfer augments intracellular tetrahydrobiopterin in human endothelial cells: effects on nitric oxide synthase activity, protein levels and dimerisation Cardiovasc Res, September 1, 2002; 55(4): 838 - 849. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Hyndman, S. Verma, R. J. Rosenfeld, T. J. Anderson, and H. G. Parsons Interaction of 5-methyltetrahydrofolate and tetrahydrobiopterin on endothelial function Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2167 - H2172. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hattori, N. Nakanishi, and K. Kasai Statin enhances cytokine-mediated induction of nitric oxide synthesis in vascular smooth muscle cells Cardiovasc Res, June 1, 2002; 54(3): 649 - 658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sun, K. P. Patel, and W. G. Mayhan Tetrahydrobiopterin, a cofactor for NOS, improves endothelial dysfunction during chronic alcohol consumption Am J Physiol Heart Circ Physiol, November 1, 2001; 281(5): H1863 - H1869. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Gori, J. M. Burstein, S. Ahmed, S. E.S. Miner, A. Al-Hesayen, S. Kelly, and J. D. Parker Folic Acid Prevents Nitroglycerin-Induced Nitric Oxide Synthase Dysfunction and Nitrate Tolerance: A Human In Vivo Study Circulation, September 4, 2001; 104(10): 1119 - 1123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Marinos, W. Zhang, G. Wu, K. A. Kelly, and C. J. Meininger Tetrahydrobiopterin levels regulate endothelial cell proliferation Am J Physiol Heart Circ Physiol, August 1, 2001; 281(2): H482 - H489. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. P. Tiefenbacher Tetrahydrobiopterin: a critical cofactor for eNOS and a strategy in the treatment of endothelial dysfunction? Am J Physiol Heart Circ Physiol, June 1, 2001; 280(6): H2484 - H2488. [Full Text] [PDF]
|
|
|
|
 |
|
 A.H. Henderson 'It all used to be so simple in the old days'. A personal view Eur. Heart J., April 2, 2001; 22(8): 648 - 653. [PDF]
|
|
|
|
|
|
F. Cosentino, J. E. Barker, M. P. Brand, S. J. Heales, E. R. Werner, J. R. Tippins, N. West, K. M. Channon, M. Volpe, and T. F. Luscher Reactive Oxygen Species Mediate Endothelium-Dependent Relaxations in Tetrahydrobiopterin-Deficient Mice Arterioscler Thromb Vasc Biol, April 1, 2001; 21(4): 496 - 502. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Verma, L. Yao, D. J. Stewart, A. S. Dumont, T. J. Anderson, and J. H. McNeill Endothelin Antagonism Uncovers Insulin-Mediated Vasorelaxation In Vitro and In Vivo Hypertension, February 1, 2001; 37(2): 328 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Verma, F. Lovren, A. S. Dumont, K. J. Mather, A. Maitland, T. M. Kieser, C. R. Triggle, and T. J. Anderson Tetrahydrobiopterin improves endothelial function in human saphenous veins J. Thorac. Cardiovasc. Surg., October 1, 2000; 120(4): 668 - 671. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Brunner, G. Wolkart, S. Pfeiffer, J. C Russell, and T. C Wascher Vascular dysfunction and myocardial contractility in the JCR:LA-corpulent rat Cardiovasc Res, July 1, 2000; 47(1): 150 - 158. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Golser, A. C. F. Gorren, A. Leber, P. Andrew, H.-J. Habisch, E. R. Werner, K. Schmidt, R. C. Venema, and B. Mayer Interaction of Endothelial and Neuronal Nitric-oxide Synthases with the Bradykinin B2 Receptor. BINDING OF AN INHIBITORY PEPTIDE TO THE OXYGENASE DOMAIN BLOCKS UNCOUPLED NADPH OXIDATION J. Biol. Chem., February 25, 2000; 275(8): 5291 - 5296. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Hyndman, S. Verma, R. J. Rosenfeld, T. J. Anderson, and H. G. Parsons Interaction of 5-methyltetrahydrofolate and tetrahydrobiopterin on endothelial function Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2167 - H2172. [Abstract] [Full Text] [PDF]
|
|