© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Role of superoxide anion in the pathogenesis of cytokine-induced myocardial dysfunction in dogs in vivo1
aThe Research Institute of Angiocardiology, Kyushu University School of Medicine, Fukuoka, Japan
bThe Department of Physiology, Tokai University School of Medicine, Isehara, Japan
* Corresponding author. Fax: +81-92-642-5374. E-mail address: shimo@cardiol.med.kyushu-u.ac.jp (H. Shimokawa)
Objective: Although studies in vitro have implicated oxygen-derived free radicals as possible mediators of inflammatory cytokine-induced cell injury, the role of the radicals in the cytokine-induced myocardial dysfunction in vivo remains unclear. The present study was designed to address this point in our novel canine model of cytokine-induced myocardial dysfunction in vivo. Methods: Studies were performed in mongrel dogs, in which microspheres (MS, 15 µm in diameter) with and without interleukin-1β (IL-1β) were injected into the left main coronary artery (control and IL-1β group). Left ventricular ejection fraction (LVEF) was evaluated by echocardiography for 1 week. Results: Immediately after the intracoronary injection of MS (106/kg), LVEF equally decreased to approximately 30% in both the control and IL-1β group. While LVEF rapidly recovered within 2 days in the control group, it remained depressed in the IL-1β group until day 7 (p<0.0001 vs. control group). Pretreatment with OPC-6535 (an inhibitor of superoxide production) before (2 mg/kg IV) and 1 and 2 days after IL-1β MS application (1 mg/kg IV) prevented the IL-1β-induced myocardial dysfunction. Superoxide production in the myocardium was significantly higher in the IL-1β group than in the control group at day 2 (p<0.01), and OPC-6535 significantly suppressed the IL-1β-induced superoxide production (p<0.01). An HPLC assay showed that nitrotyrosine, a marker of the formation of peroxynitrite by superoxide anion and nitric oxide, was present in the myocardium treated with IL-1β but not in that with control MS. OPC-6535 abolished the IL-1β-induced formation of myocardial nitrotyrosine. Conclusion: These results indicate that superoxide anion and the resultant formation of peroxynitrite may substantially be involved in the pathogenesis of the cytokine-induced myocardial dysfunction in dogs in vivo.
KEYWORDS Cytokines; Free radicals; Heart failure; Myocytes; Nitric oxide
1 This work was presented in part at the 70th Scientific Sessions of the American Heart Association, Orlando, Florida, November 9–12, 1997.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Casadevall, C. Coronell, A. L. Ramirez-Sarmiento, J. Martinez-Llorens, E. Barreiro, M. Orozco-Levi, J. Gea, and on behalf of the ENIGMA in COPD group Upregulation of pro-inflammatory cytokines in the intercostal muscles of COPD patients Eur. Respir. J., October 1, 2007; 30(4): 701 - 707. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pacher, J. S. Beckman, and L. Liaudet Nitric Oxide and Peroxynitrite in Health and Disease Physiol Rev, January 1, 2007; 87(1): 315 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Paolocci Peroxynitrite like Pan? Cardiovasc Res, August 1, 2005; 67(2): 176 - 178. [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Chen, M. Hou, Y. Li, J. H. Traverse, P. Zhang, D. Salvemini, T. Fukai, and R. J. Bache Increased superoxide production causes coronary endothelial dysfunction and depressed oxygen consumption in the failing heart Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H133 - H141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D. Prabhu Cytokine-Induced Modulation of Cardiac Function Circ. Res., December 10, 2004; 95(12): 1140 - 1153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Berthonneche, T. Sulpice, F. Boucher, L. Gouraud, J. de Leiris, S. E. O'Connor, J.-M. Herbert, and P. Janiak New insights into the pathological role of TNF-{alpha} in early cardiac dysfunction and subsequent heart failure after infarction in rats Am J Physiol Heart Circ Physiol, July 1, 2004; 287(1): H340 - H350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. V. Turko and F. Murad Protein Nitration in Cardiovascular Diseases Pharmacol. Rev., December 1, 2002; 54(4): 619 - 634. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. J. Thannickal and B. L. Fanburg Reactive oxygen species in cell signaling Am J Physiol Lung Cell Mol Physiol, December 1, 2000; 279(6): L1005 - L1028. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Macarthur, T. C. Westfall, D. P. Riley, T. P. Misko, and D. Salvemini Inactivation of catecholamines by superoxide gives new insights on the pathogenesis of septic shock PNAS, August 15, 2000; 97(17): 9753 - 9758. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D. Prabhu, B. Chandrasekar, D. R. Murray, and G. L. Freeman {beta}-Adrenergic Blockade in Developing Heart Failure : Effects on Myocardial Inflammatory Cytokines, Nitric Oxide, and Remodeling Circulation, May 2, 2000; 101(17): 2103 - 2109. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Bkaily and P. D'orleans-Juste Cytokine-induced free radicals and their roles in myocardial dysfunctions Cardiovasc Res, June 1, 1999; 42(3): 576 - 577. [Full Text] [PDF]
|
|