Skip Navigation

Cardiovascular Research 2003 57(3):853-860; doi:10.1016/S0008-6363(02)00779-4
© 2003 by European Society of Cardiology
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Miller, M. R
Right arrow Articles by Megson, I. L
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Miller, M. R
Right arrow Articles by Megson, I. L
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 2003, European Society of Cardiology

A novel S-nitrosothiol causes prolonged and selective inhibition of platelet adhesion at sites of vascular injury

Mark R Millera, Inderraj S Hanspala, Patrick W.F Hadokea, David E Newbya, Adriano G Rossib, David J Webba and Ian L Megsona,*

aCentre for Cardiovascular Science, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK
bMRC Centre for Inflammation Research, University of Edinburgh, Edinburgh EH8 9AG, UK

* Corresponding author. Tel.: +44-131-651-1193; fax: +44-131-650-6527. ian.megson{at}ed.ac.uk

Objective: Platelet adhesion to areas of endothelial denudation following angioplasty is an important factor contributing to the limitations of this technique. Lipophilic S-nitrosothiols like S-nitroso-N-valerylpenicillamine (SNVP) are novel nitric oxide (NO) donor drugs with anti-platelet and vasodilator properties that are selective for areas of endothelial denudation. Here we assess the inhibitory effect of SNVP on platelet adhesion to angioplastied rabbit carotid arteries. Methods: A rabbit model was used to measure adhesion of radiolabelled platelets to carotid arteries following balloon angioplasty. The effects of SNVP were compared to the conventional NO donor, nitroglycerin (NTG). Electron microscopy was used to visualize adhering platelets. Results: Angioplasty resulted in endothelial denudation with only a modest reduction in vessel contractility. In vivo administration of NTG and SNVP (both 200 nmol) prevented the hyper-aggregability (~20%) of circulating platelets caused by angioplasty. However, bolus NTG failed to inhibit adhesion of radiolabelled platelets 30 min after angioplasty, despite inducing a transient 30% reduction in systemic blood pressure. In contrast, equimolar SNVP had little effect on blood pressure but markedly inhibited platelet adhesion (62% compared to control; P=0.003). Platelet adhesion was confirmed with electron microscopy. Conclusion: The prolonged effects of SNVP at sites of endothelial damage suggest that novel S-nitrosothiols might offer a means of targeted delivery of an antiplatelet agent to areas of vascular injury.

KEYWORDS ACh, acetylcholine; ADP, adenosine 5'-diphosphate; Hep-Sal, heparinised saline; L-NAME, N{omega}-nitro-L-arginine methyl ester; NO, nitric oxide; NTG, nitroglycerin; PE, phenylephrine; PRP, platelet rich plasma; SNVP, S-nitroso-N-valerylpenicillamine


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


This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Marcondes, M. H. M. Cardoso, R. P. Morganti, S. M. Thomazzi, S. Lilla, F. Murad, G. De Nucci, and E. Antunes
Cyclic GMP-independent mechanisms contribute to the inhibition of platelet adhesion by nitric oxide donor: A role for {alpha}-actinin nitration
PNAS, February 28, 2006; 103(9): 3434 - 3439.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.