Cardiovascular Research

Cardiovascular Research 1998 38(2):485-492; doi:10.1016/S0008-6363(98)00017-0
© 1998 by European Society of Cardiology

This Article Full Text FREE Full Text (PDF) E-letters: Submit a response Alert me when this article is cited Alert me when E-letters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Request Permissions Disclaimer Google Scholar Articles by Newby, D. E Articles by Webb, D. J Search for Related Content PubMed PubMed Citation Articles by Newby, D. E Articles by Webb, D. J Social Bookmarking          What's this?

Copyright © 1998, European Society of Cardiology

The L-arginine/nitric oxide pathway contributes to the acute release of tissue plasminogen activator in vivo in man

David E Newby^a,b,*, Robert A Wright^b, Pamela Dawson^c, Christopher A Ludlam^c, Nicholas A Boon^b, Keith A.A Fox^b and David J Webb^a

^aClinical Pharmacology Unit and Research Centre, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK
^bDepartment of Cardiology, University of Edinburgh, Royal Infirmary, Lauriston Place, Edinburgh EH3 9YW, UK
^cDepartment of Haematology, University of Edinburgh, Royal Infirmary, Lauriston Place, Edinburgh EH3 9YW, UK

^* Corresponding author. Tel.: +44 (131) 332-1205; Fax: +44 (131) 343-6017; E-mail: d.e.newby@ed.ac.uk

Objective: Effective endogenous fibrinolysis requires rapid release of endothelial tissue plasminogen activator (t-PA). Using the nitric oxide synthase inhibitor, L-N^G-monomethylarginine (L-NMMA), we examined the contribution of endogenous nitric oxide to substance P-induced t-PA release in vivo in man. Methods: Blood flow and plasma fibrinolytic and haemostatic factors were measured in both forearms of 8 healthy male volunteers who received unilateral brachial artery infusions of substance P (2–8 pmol/min) and L-NMMA (1–4 µg/min). Results: Substance P caused dose-dependent increases in blood flow (P<0.001) and plasma t-PA antigen (P=0.04) and activity (P<0.001) concentrations confined to the infused forearm, but had no effect on plasminogen activator inhibitor type 1 (PAI-1) or von Willebrand factor concentrations. In the presence of L-NMMA, substance P again caused significant increases in blood flow (P<0.001) and t-PA antigen (P=0.003) and activity (P<0.001) concentrations but these increases were significantly less than with substance P alone (P<0.001, P=0.05 and P<0.01, respectively). L-NMMA alone significantly reduced blood flow in the infused arm, but had no measurable effect on t-PA or PAI-1 concentrations. Conclusions: The L-arginine/nitric oxide pathway contributes to substance P-induced t-PA release in vivo in man. This provides an important potential mechanism whereby endothelial dysfunction increases the risk of atherothrombosis through a reduction in the acute fibrinolytic capacity.

KEYWORDS Thrombolysis; Endothelial factor; Nitric oxide; Blood flow; Endothelial function

CiteULike    Connotea    Del.icio.us    What's this?

This article has been cited by other articles:

				C. Giannarelli, A. Virdis, F. De Negri, A. Magagna, E. Duranti, A. Salvetti, and S. Taddei Effect of Sulfaphenazole on Tissue Plasminogen Activator Release in Normotensive Subjects and Hypertensive Patients Circulation, March 31, 2009; 119(12): 1625 - 1633. [Abstract] [Full Text] [PDF]

				C. Giannarelli, A. Virdis, F. De Negri, E. Duranti, A. Magagna, L. Ghiadoni, A. Salvetti, and S. Taddei Tissue-Type Plasminogen Activator Release in Healthy Subjects and Hypertensive Patients: Relationship With {beta}-Adrenergic Receptors and the Nitric Oxide Pathway Hypertension, August 1, 2008; 52(2): 314 - 321. [Abstract] [Full Text] [PDF]

				C. Giannarelli, F. De Negri, A. Virdis, L. Ghiadoni, A. Cipriano, A. Magagna, S. Taddei, and A. Salvetti Nitric Oxide Modulates Tissue Plasminogen Activator Release in Normotensive Subjects and Hypertensive Patients Hypertension, April 1, 2007; 49(4): 878 - 884. [Abstract] [Full Text] [PDF]

				S D Robinson, C A Ludlam, N A Boon, and D E Newby Phosphodiesterase type 5 inhibition does not reverse endothelial dysfunction in patients with coronary heart disease Heart, February 1, 2006; 92(2): 170 - 176. [Abstract] [Full Text] [PDF]

				J. H. Fischer and M. Steinhoff Effects of aprotinin on endothelium-dependent relaxation of large coronary arteries Eur. J. Cardiothorac. Surg., December 1, 2005; 28(6): 801 - 804. [Abstract] [Full Text] [PDF]

				J. J. Oliver, D. J. Webb, and D. E. Newby Stimulated Tissue Plasminogen Activator Release as a Marker of Endothelial Function in Humans Arterioscler Thromb Vasc Biol, December 1, 2005; 25(12): 2470 - 2479. [Abstract] [Full Text] [PDF]

				V. F. Tapson The Role of Smoking in Coagulation and Thromboembolism in Chronic Obstructive Pulmonary Disease Proceedings of the ATS, April 1, 2005; 2(1): 71 - 77. [Abstract] [Full Text] [PDF]

				J. A. Adams, J. Bassuk, D. Wu, M. Grana, P. Kurlansky, and M. A. Sackner Periodic acceleration: effects on vasoactive, fibrinolytic, and coagulation factors J Appl Physiol, March 1, 2005; 98(3): 1083 - 1090. [Abstract] [Full Text] [PDF]

				B. E. Sobel, D. J. Taatjes, and D. J. Schneider Intramural Plasminogen Activator Inhibitor Type-1 and Coronary Atherosclerosis Arterioscler Thromb Vasc Biol, November 1, 2003; 23(11): 1979 - 1989. [Abstract] [Full Text] [PDF]

				S. Chia, C. A. Ludlam, K. A. A. Fox, and D. E. Newby Acute systemic inflammation enhances endothelium-dependent tissue plasminogen activator release in men J. Am. Coll. Cardiol., January 15, 2003; 41(2): 333 - 339. [Abstract] [Full Text] [PDF]

				F. N. Witherow, P. Dawson, C. A. Ludlam, K. A. A. Fox, and D. E. Newby Marked bradykinin-induced tissue plasminogen activator release in patients with heart failure maintained on long-term angiotensin-converting enzyme inhibitor therapy J. Am. Coll. Cardiol., September 4, 2002; 40(5): 961 - 966. [Abstract] [Full Text] [PDF]

				J. P.J. Halcox, W. H. Schenke, G. Zalos, R. Mincemoyer, A. Prasad, M. A. Waclawiw, K. R.A. Nour, and A. A. Quyyumi Prognostic Value of Coronary Vascular Endothelial Dysfunction Circulation, August 6, 2002; 106(6): 653 - 658. [Abstract] [Full Text] [PDF]

				M. M. Arriero, J. C. de la Pinta, M. Escribano, A. Celdran, L. Munoz-Alameda, J. Garcia-Canete, A. M. Jimenez, S. Casado, J. Farre, and A. Lopez-Farre Aspirin Prevents Escherichia coli Lipopolysaccharide- and Staphylococcus aureus-Induced Downregulation of Endothelial Nitric Oxide Synthase Expression in Guinea Pig Pericardial Tissue Circ. Res., April 5, 2002; 90(6): 719 - 727. [Abstract] [Full Text] [PDF]

				D E Newby, F N Witherow, R A Wright, P Bloomfield, C A Ludlam, N A Boon, K A A Fox, and D J Webb Hypercholesterolaemia and lipid lowering treatment do not affect the acute endogenous fibrinolytic capacity in vivo Heart, January 1, 2002; 87(1): 48 - 53. [Abstract] [Full Text] [PDF]

				D. E. Newby, A. L. McLeod, N. G. Uren, L. Flint, C. A. Ludlam, D. J. Webb, K. A. A. Fox, and N. A. Boon Impaired Coronary Tissue Plasminogen Activator Release Is Associated With Coronary Atherosclerosis and Cigarette Smoking : Direct Link Between Endothelial Dysfunction and Atherothrombosis Circulation, April 17, 2001; 103(15): 1936 - 1941. [Abstract] [Full Text] [PDF]

				N. J. Brown, J. V. Gainer, L. J. Murphey, and D. E. Vaughan Bradykinin Stimulates Tissue Plasminogen Activator Release From Human Forearm Vasculature Through B2 Receptor-Dependent, NO Synthase-Independent, and Cyclooxygenase-Independent Pathway Circulation, October 31, 2000; 102(18): 2190 - 2196. [Abstract] [Full Text] [PDF]

				M. M. ARRIERO, J. A. RODRÍGUEZ-FEO, A. CELDRÁN, L. S. D. MIGUEL, F. GONZÁLEZ-FERNÁNDEZ, J. FORTES, A. REYERO, O. FRIEYRO, J. C. D. L. PINTA, A. FRANCO, et al. Expression of Endothelial Nitric Oxide Synthase in Human Peritoneal Tissue: Regulation by Escherichia Coli Lipopolysaccharide J. Am. Soc. Nephrol., October 1, 2000; 11(10): 1848 - 1856. [Abstract] [Full Text]

				C. Labinjoh, D. E. Newby, P. Dawson, N. R. Johnston, C. A. Ludlam, N. A. Boon, and D. J. Webb Fibrinolytic actions of intra-arterial angiotensin II and bradykinin in vivo in man Cardiovasc Res, September 1, 2000; 47(4): 707 - 714. [Abstract] [Full Text] [PDF]

				N. J. Brown, J. V. Gainer, C. M. Stein, and D. E. Vaughan Bradykinin Stimulates Tissue Plasminogen Activator Release in Human Vasculature Hypertension, June 1, 1999; 33(6): 1431 - 1435. [Abstract] [Full Text] [PDF]

				D. E. Newby, R. A. Wright, C. Labinjoh, C. A. Ludlam, K. A. A. Fox, N. A. Boon, and D. J. Webb Endothelial Dysfunction, Impaired Endogenous Fibrinolysis, and Cigarette Smoking : A Mechanism for Arterial Thrombosis and Myocardial Infarction Circulation, March 23, 1999; 99(11): 1411 - 1415. [Abstract] [Full Text] [PDF]

				M. M. Arriero, J. C. de la Pinta, M. Escribano, A. Celdran, L. Munoz-Alameda, J. Garcia-Canete, A. M. Jimenez, S. Casado, J. Farre, and A. Lopez-Farre Aspirin Prevents Escherichia coli Lipopolysaccharide- and Staphylococcus aureus-Induced Downregulation of Endothelial Nitric Oxide Synthase Expression in Guinea Pig Pericardial Tissue Circ. Res., April 5, 2002; 90(6): 719 - 727. [Abstract] [Full Text] [PDF]

Online ISSN 1755-3245 - Print ISSN 0008-6363

Copyright © 2009 European Society of Cardiology

Oxford Journals Oxford University Press

• Site Map
• Privacy Policy
• Frequently Asked Questions

Other Oxford University Press sites: Oxford University Press Oxford Journals China Oxford Journals Japan American National Biography Booksellers' Information Service Children's Fiction and Poetry Children's Reference Corporate & Special Sales Dictionaries Dictionary of National Biography Digital Reference English Language Teaching Higher Education Textbooks Humanities International Education Unit Law Medicine Music Online Products Oxford English Dictionary Reference Rights and Permissions Science School Books Social Sciences Very Short Introductions World's Classics