![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Vol. 297, Issue 1, 380-387, April 2001
Departments of Pharmacological Sciences (G.R.) and Pharmacology,
Chemotherapy, and Medical Toxicology (G.R., B.M., V.D.G.C.), University
of Milan, Milan, Italy; and Department of Experimental Medicine,
Environmental and Biotechnology, University of Milano-Bicocca, Monza,
Italy (M.B., F.B.)
NCX 4016, a nitro-ester of aspirin endowed with antithrombotic
activity, appears to have clinical potential in treating cardiac complications related to coronary insufficiency. This compound has been
shown to improve postischemic ventricular dysfunction and to reduce
myocardial infarct size in the rabbit. The cardioprotection conferred
by NCX 4016 (10, 30, and 100 mg/kg) and aspirin (ASA, 54 mg/kg) was
evaluated in anesthetized rats subjected to 30 min of myocardial
ischemia followed by 120 min of reperfusion (MI/R). Drugs were given
orally for 5 consecutive days. NCX 4016 displayed remarkable
cardioprotection in rats subjected to MI/R as was evident in the
reduction of ventricular premature beats and in the incidence of
ventricular tachycardia and fibrillation; they were reduced dose
dependently and correlated with survival of all rats treated with the
higher dose of NCX 4016. In these animals, infarct size was restricted
proportionally to the dose of NCX 4016 associated with diminution of
both plasma creatine phosphokinase and cardiac myeloperoxidase
activities. ASA showed only a minor degree of protection against MI/R
damage. Rats treated with
NG-nitro-L-arginine methyl ester
(L-NAME, 10 mg/kg) demonstrated aggravated myocardial
damage in terms of arrhythmias, mortality, and infarct size.
Supplementation of nitric oxide (NO) with NCX 4016 (100 mg/kg) greatly
reduced the worsening effect caused by L-NAME. The
beneficial effects of NCX 4016 appear to derive in large part from the
NO moiety, which modulates a number of cellular events leading to
inflammation, obstruction of the coronary microcirculation, arrhythmias, and myocardial necrosis.
This article has been cited by other articles:
|
|
 |
|
  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]
|
|
|
|
 |
|
 M. V. Cohen, X.-M. Yang, and J. M. Downey Nitric oxide is a preconditioning mimetic and cardioprotectant and is the basis of many available infarct-sparing strategies Cardiovasc Res, May 1, 2006; 70(2): 231 - 239. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. G. Burke, C. L. Wainwright, I. Vojnovic, T. Warner, D. G. Watson, and B. L. Furman The Effect of NCX4016 [2-Acetoxy-benzoate 2-(2-nitroxymethyl)-phenyl Ester] on the Consequences of Ischemia and Reperfusion in the Streptozotocin Diabetic Rat J. Pharmacol. Exp. Ther., March 1, 2006; 316(3): 1107 - 1114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Goligorsky Endothelial cell dysfunction: can't live with it, how to live without it Am J Physiol Renal Physiol, May 1, 2005; 288(5): F871 - F880. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Emanueli, S. Van Linthout, M. B. Salis, A. Monopoli, P. Del Soldato, E. Ongini, and P. Madeddu Nitric Oxide-Releasing Aspirin Derivative, NCX 4016, Promotes Reparative Angiogenesis and Prevents Apoptosis and Oxidative Stress in a Mouse Model of Peripheral Ischemia Arterioscler. Thromb. Vasc. Biol., November 1, 2004; 24(11): 2082 - 2087. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Rossoni, B. Manfredi, P. Del Soldato, and F. Berti The Nitric Oxide-Releasing Naproxen Derivative Displays Cardioprotection in Perfused Rabbit Heart Submitted to Ischemia-Reperfusion J. Pharmacol. Exp. Ther., August 1, 2004; 310(2): 555 - 562. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. R. Gross, A. K. Hsu, and G. J. Gross Acute Aspirin Treatment Abolishes, whereas Acute Ibuprofen Treatment Enhances Morphine-Induced Cardioprotection: Role of 12-Lipoxygenase J. Pharmacol. Exp. Ther., July 1, 2004; 310(1): 185 - 191. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Wallace, M. N. Muscara, G. de Nucci, S. Zamuner, G. Cirino, P. del Soldato, and E. Ongini Gastric Tolerability and Prolonged Prostaglandin Inhibition in the Brain with a Nitric Oxide-Releasing Flurbiprofen Derivative, NCX-2216 [3-[4-(2-Fluoro-{alpha}-methyl-[1,1'-biphenyl]-4-acetyloxy)-3-methoxyphenyl]-2-propenoic acid 4-nitrooxy butyl ester] J. Pharmacol. Exp. Ther., May 1, 2004; 309(2): 626 - 633. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bertuglia, A. Giusti, and P. Del Soldato Antioxidant activity of nitro derivative of aspirin against ischemia-reperfusion in hamster cheek pouch microcirculation Am J Physiol Gastrointest Liver Physiol, March 1, 2004; 286(3): G437 - G443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Fiorucci, A. Mencarelli, A. Meneguzzi, A. Lechi, A. Morelli, P. del Soldato, and P. Minuz NCX-4016 (NO-Aspirin) Inhibits Lipopolysaccharide-Induced Tissue Factor Expression In Vivo: Role of Nitric Oxide Circulation, December 10, 2002; 106(24): 3120 - 3125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Napoli, G. Aldini, J. L. Wallace, F. de Nigris, R. Maffei, P. Abete, D. Bonaduce, G. Condorelli, F. Rengo, V. Sica, et al. Efficacy and age-related effects of nitric oxide-releasing aspirin on experimental restenosis PNAS, January 24, 2002; (2002) 22639399. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Napoli, G. Aldini, J. L. Wallace, F. de Nigris, R. Maffei, P. Abete, D. Bonaduce, G. Condorelli, F. Rengo, V. Sica, et al. Efficacy and age-related effects of nitric oxide-releasing aspirin on experimental restenosis PNAS, February 5, 2002; 99(3): 1689 - 1694. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
