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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on October 31, 2005; DOI: 10.1124/jpet.105.096339

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Received for publication September 27, 2005.
Revised October 28, 2005.
Accepted for publication October 28, 2005.

The effect of NCX4016 on the consequences of ischaemia and reperfusion in the streptozotocin diabetic rat

Steven Burke 1, Cherry Wainwright 2, Ivana Vojnovic 3, Timothy Warner 3, David Watson 4, Brian Furman 4*

1 University of Strathclyde 2 The Robert Gordon University 3 The William Harvey Research Institute 4 Strathclyde University

* Address correspondence to: E-mail: b.l.furman{at}strath.ac.uk

Abstract

The aim of this study was to assess the effect of chronic administration of NCX4016, a nitric oxide- releasing aspirin derivative on the consequences of coronary artery occlusion in streptozotocin-diabetic rats. Rats were made diabetic by injection of streptozotocin (60 mg kg-1) and received insulin (2.5 U kg-1 s.c.), daily for 4 weeks. Animals received (i) Vehicle (PEG400 1ml kg-1), (ii) aspirin (65.2mg kg-1), (iii) NCX4016 (60mg kg-1), or (iv) NCX4016 (120mg kg-1) orally, once daily for the last 5 days before coronary artery occlusion (CAO). One hour following the last dose, pentobarbitone-anaesthetised rats were subjected to CAO for 30-min followed by 120-min reperfusion. Neither drug significantly modified initial hemodynamics or plasma glucose levels compared to vehicle treatment in either non-diabetic or diabetic rats. Neither drug modified the total ventricular premature beats (VPB) count in normal animals, although NCX4016, but not aspirin, reduced the total VPB count and the incidence of ventricular tachycardia in diabetic rats. In non- diabetic animals, both aspirin and NCX4016 reduced infarct size. However, in diabetic rats infarct size was reduced only by the larger dose of NCX4016 (120 mg/kg-1) but not by aspirin or the lower dose of NCX4016. These results demonstrate that the cardioprotective effects of NCX4016 are reduced in the presence of diabetes compared to the effects seen in non-diabetic animals. In summary, the present study confirms the protective effect of NCX4016 against ischaemia- reperfusion injury in the normal rat heart and demonstrates for the first time its protective effect in the heart of streptozotocin-diabetic rats.


Key words: NCX4016, aspirin, diabetes, ischemia, myocardial, streptozotocin


This article has been cited by other articles:


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 Am. J. Physiol. Heart Circ. Physiol.Home page
Y. Fu, Z. Wang, W. L. Chen, P. K. Moore, and Y. Z. Zhu
Cardioprotective effects of nitric oxide-aspirin in myocardial ischemia-reperfused rats
Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1545 - H1552.
[Abstract] [Full Text] [PDF]


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