| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Cardiothoracic Research Laboratory, Carlyle Fraser Heart Center, Crawford Long Hospital of Emory University, Atlanta, Georgia 30365; and 2 Division of Cardiology, University of Louisville, Louisville, Kentucky 40292
This study tested the hypothesis that A3 adenosine receptors inhibit neutrophil (PMN) function and PMN-mediated reperfusion injury. 2-Chloro-N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide (Cl-IB-MECA), an A3 agonist, did not attenuate superoxide production or myeloperoxidase release from stimulated PMNs. However, Cl-IB-MECA reduced platelet-activating factor-stimulated PMN adherence to coronary endothelium at low concentrations: 52 ± 27, 45 ± 10, and 87 ± 23 PMNs/mm2 at 0.1, 1.0, and 10 nM vs. 422 ± 64 PMNs/mm2 with platelet-activating factor alone. This inhibition was not blocked by A1 (5 µM KW-3902) or A2a (5 µM KF-21326) antagonists: 44 ± 3 and 43 ± 2 PMNs/mm2, respectively. Endothelial pretreatment with 1 nM Cl-IB-MECA reduced PMN adherence, which was reversed by the A3 antagonist MRS-1220 (100 nM). PMN-mediated reperfusion injury was initiated in isolated rabbit hearts by infusion of 28 × 106 PMNs/min for 10 min early in reperfusion. PMNs caused a significant decrease in recovery of left ventricular developed pressure and positive and negative time derivatives of pressure (23 ± 3, 25 ± 3, and 23 ± 3% of baseline, respectively) vs. buffer-perfused hearts (43 ± 7, 44 ± 7, and 45 ± 6%, respectively). Cl-IB-MECA (10 nM) given at reperfusion attenuated the PMN-mediated loss of contractile recovery (40 ± 3, 46 ± 5, and 42 ± 4% of baseline). Cl-IB-MECA reduced myeloperoxidase release activity (5.3 ± 0.6 absorbance units/min) and CD18-positive cells (54 ± 9 cells/slide) compared with the untreated PMN group (17.9 ± 1.7 absorbance units/min and 183 ± 68 cells/slide). We conclude that Cl-IB-MECA attenuates reperfusion injury by decreasing PMN-endothelial cell interactions. These results suggest that the A3 adenosine receptor may be a novel therapeutic target for treatment of myocardial ischemia and reperfusion.
endothelial adherence; superoxide; myeloperoxidase; CD18
This article has been cited by other articles:
|
|
 |
|
  R. A. G. Patel, D. K. Glover, A. Broisat, H. K. Kabul, M. Ruiz, N. C. Goodman, C. M. Kramer, D. J. Meerdink, J. Linden, and G. A. Beller Reduction in myocardial infarct size at 48 hours after brief intravenous infusion of ATL-146e, a highly selective adenosine A2A receptor agonist Am J Physiol Heart Circ Physiol, August 1, 2009; 297(2): H637 - H642. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. C. Wan, Z.-D. Ge, A. Tampo, Y. Mio, M. W. Bienengraeber, W. R. Tracey, G. J. Gross, W.-M. Kwok, and J. A. Auchampach The A3 Adenosine Receptor Agonist CP-532,903 [N6-(2,5-Dichlorobenzyl)-3'-aminoadenosine-5'-N-methylcarboxamide] Protects against Myocardial Ischemia/Reperfusion Injury via the Sarcolemmal ATP-Sensitive Potassium Channel J. Pharmacol. Exp. Ther., January 1, 2008; 324(1): 234 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Moses, P. D. Addison, P. C. Neligan, H. Ashrafpour, N. Huang, S. E. McAllister, J. E. Lipa, C. R. Forrest, and C. Y. Pang Inducing late phase of infarct protection in skeletal muscle by remote preconditioning: efficacy and mechanism Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2005; 289(6): R1609 - R1617. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kin, A. J. Zatta, M. T. Lofye, B. S. Amerson, M. E. Halkos, F. Kerendi, Z.-Q. Zhao, R. A. Guyton, J. P. Headrick, and J. Vinten-Johansen Postconditioning reduces infarct size via adenosine receptor activation by endogenous adenosine Cardiovasc Res, July 1, 2005; 67(1): 124 - 133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. R. Tracey, W. P. Magee, J. J. Oleynek, R. J. Hill, A. H. Smith, D. M. Flynn, and D. R. Knight Novel N6-substituted adenosine 5'-N-methyluronamides with high selectivity for human adenosine A3 receptors reduce ischemic myocardial injury Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2780 - H2787. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Headrick, B. Hack, and K. J. Ashton Acute adenosinergic cardioprotection in ischemic-reperfused hearts Am J Physiol Heart Circ Physiol, November 1, 2003; 285(5): H1797 - H1818. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Auchampach, Z.-D. Ge, T. C. Wan, J. Moore, and G. J. Gross A3 adenosine receptor agonist IB-MECA reduces myocardial ischemia-reperfusion injury in dogs Am J Physiol Heart Circ Physiol, July 11, 2003; 285(2): H607 - H613. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. L. Maddock, M. M. Mocanu, and D. M. Yellon Adenosine A3 receptor activation protects the myocardium from reperfusion/reoxygenation injury Am J Physiol Heart Circ Physiol, October 1, 2002; 283(4): H1307 - H1313. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. R. Cross, E. Murphy, R. G. Black, J. Auchampach, and C. Steenbergen Overexpression of A3 adenosine receptors decreases heart rate, preserves energetics, and protects ischemic hearts Am J Physiol Heart Circ Physiol, October 1, 2002; 283(4): H1562 - H1568. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. B. Fredholm, A. P. IJzerman, K. A. Jacobson, K.-N. Klotz, and J. Linden International Union of Pharmacology. XXV. Nomenclature and Classification of Adenosine Receptors Pharmacol. Rev., December 1, 2001; 53(4): 527 - 552. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Cerniway, Z. Yang, M. A. Jacobson, J. Linden, and G. P. Matherne Targeted deletion of A3 adenosine receptors improves tolerance to ischemia-reperfusion injury in mouse myocardium Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1751 - H1758. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Kilpatrick, P. Narayan, R. M. Mentzer Jr., and R. D. Lasley Adenosine A3 agonist cardioprotection in isolated rat and rabbit hearts is blocked by the A1 antagonist DPCPX Am J Physiol Heart Circ Physiol, August 1, 2001; 281(2): H847 - H853. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Muraki, C. D. Morris, J. M. Budde, D. A. Velez, Z.-Q. Zhao, R. A. Guyton, and J. Vinten-Johansen Experimental off-pump coronary artery revascularization with adenosine-enhanced reperfusion J. Thorac. Cardiovasc. Surg., March 1, 2001; 121(3): 570 - 579. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. McCully, Y. Toyoda, M. Uematsu, R. D. Stewart, and S. Levitsky Adenosine-enhanced ischemic preconditioning: adenosine receptor involvement during ischemia and reperfusion Am J Physiol Heart Circ Physiol, February 1, 2001; 280(2): H591 - H602. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. H. Thourani, S. S. Brar, T. P. Kennedy, L. R. Thornton, J. A. Watts, R. S. Ronson, Z.-Q. Zhao, A. L. Sturrock, J. R. Hoidal, and J. Vinten-Johansen Nonanticoagulant heparin inhibits NF-kappa B activation and attenuates myocardial reperfusion injury Am J Physiol Heart Circ Physiol, June 1, 2000; 278(6): H2084 - H2093. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Taira, J. Tamaoki, K. Nishimura, J. Nakata, M. Kondo, H. Takemura, and A. Nagai Adenosine A3 receptor-mediated potentiation of mucociliary transport and epithelial ciliary motility Am J Physiol Lung Cell Mol Physiol, March 1, 2002; 282(3): L556 - L562. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
