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Beneficial effects of a NO-releasing derivative of flurbiprofen (HCT-1026) in a rat model of vascular injury and restenosis

Maffia, P. and Ianaro, A. and Sorrentino, R. and Lippolis, L. and Maiello, F.M. and Del Soldato, P. and Ialenti, A. and Cirino, G. (2002) Beneficial effects of a NO-releasing derivative of flurbiprofen (HCT-1026) in a rat model of vascular injury and restenosis. Arteriosclerosis Thrombosis, and Vascular Biology, 22 (2). pp. 263-267. ISSN 1524-4636

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Abstract

One of the major problems related to the percutaneous transluminal coronary angioplasty technique is the renarrowing of the vessel, a phenomenon known as restenosis. NO and nonsteroidal anti-inflammatory drugs have been shown to play a role in this pathology. The main problem with the use of conventional NO donors is that they affect blood pressure and flow, and for these reasons, they cannot be used safely in clinical practice. The aim of this study was to evaluate, with the use of a rat model of balloon angioplasty, whether a structural derivative of flurbiprofen, containing an added NO-releasing moiety (HCT-1026), is able to reduce or prevent neointimal formation. Rats were treated for 14 days with equimolar doses of flurbiprofen (2, 7, and 21 mg/kg) or HCT-1026 (3, 10, and 30 mg/kg). After this 14-day treatment, HCT-1026 but not flurbiprofen significantly modified the neointima/media ratio. The reduction in the neointimal proliferation obtained with HCT-1026 was well correlated with an increase in nitrite/nitrate plasma levels and a reduced cell proliferation. Neither HCT-1026 nor flurbiprofen affected inducible NO synthase induction in injured vessels. In conclusion, HCT-1026 caused a significant reduction in restenosis that appears to be directly related to NO release. HCT-1026 may prove to be beneficial in preventing or delaying restenosis in humans.

Item type: Article
ID code: 38491
Keywords: NSAIDs , HCT-1026 , balloon angioplasty , nitric oxide , restenosis , Pharmacy and materia medica
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
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    Depositing user: Pure Administrator
    Date Deposited: 14 Mar 2012 10:35
    Last modified: 16 Jul 2013 21:28
    URI: http://strathprints.strath.ac.uk/id/eprint/38491

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