| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Critical Care Medicine, St. Jude Children's Research Hospital, Memphis, Tennessee, United States
2 Memphis, Tennessee, United States; Physiology and Biophysics, University of Tennessee, Memphis, Tennessee, United States
3 Universite Libre de Bruxelles, Institut de Recherche Interdisciplinaire en Biologie Humaine et Nucleaire, Brussels, Belgium, Belgium
4 Physiology and Pharmacology, West Virginia University Health Sciences Center, Morgantown, West Virginia, United States
5 Physiology and Biophysics, University of Tennessee, Memphis, Tennessee, United States
* To whom correspondence should be addressed. E-mail: ray.morrison{at}stjude.org.
Endogenous adenosine is an important ligand trigger for the cardioprotective effects of postconditioning (POC), yet it is unclear which adenosine receptor subtype is primarily responsible. To evaluate the role of A2A adenosine receptors in POC-induced protection, global ischemia-reperfusion was performed with and without POC in isolated wild-type (WT) and A2A adenosine receptor knockout (A2AKO) mouse hearts. Injury was measured in terms of postischemic functional recovery and release of cardiac troponin I (cTnI). Activation of protective signaling with POC was assessed by Akt and ERK1/2 phosphorylation. In WT hearts, POC improved recovery of postischemic developed pressure in early (81.6 ± 6.4 % of preischemic baseline versus 37.5 ± 5.6 % for non-POC WT at 1 min) and late reperfusion (62.2 ± 4.2 % of baseline versus 45.5 ± 5.3 % for non-POC WT at 30 min), reduced cTnI release by 37%, and doubled the phosphorylation of both Akt and ERK1/2. These beneficial effects of POC were blocked by treatment with the selective A2A adenosine receptor antagonist ZM241385 during reperfusion. Postischemic functional recovery, cTnI release and phosphorylation of Akt and ERK1/2 were not different between non-POC WT and A2AKO hearts. In A2AKO hearts, POC did not improve functional recovery, reduce cTnI release, nor increase phosphorylation of Akt or ERK1/2. Thus, the protective effects of POC are attenuated by both selective A2A receptor antagonism and targeted deletion of the gene encoding A2A adenosine receptors. These observations support the conclusion that endogenous activation of A2A adenosine receptors is an essential trigger leading to the protective effects of POC in isolated murine hearts.
This article has been cited by other articles:
|
|
 |
|
  D. A. Vessey, L. Li, N. Honbo, and J. S. Karliner Sphingosine 1-phosphate is an important endogenous cardioprotectant released by ischemic pre- and postconditioning Am J Physiol Heart Circ Physiol, October 1, 2009; 297(4): H1429 - H1435. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Musiolik, P. van Caster, A. Skyschally, K. Boengler, P. Gres, R. Schulz, and G. Heusch Reduction of infarct size by gentle reperfusion without activation of reperfusion injury salvage kinases in pigs Cardiovasc Res, August 25, 2009; (2009) cvp271v2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Skyschally, P. van Caster, K. Boengler, P. Gres, J. Musiolik, D. Schilawa, R. Schulz, and G. Heusch Ischemic Postconditioning in Pigs: No Causal Role for RISK Activation Circ. Res., January 2, 2009; 104(1): 15 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. H. Rork, K. L. Wallace, D. P. Kennedy, M. A. Marshall, A. R. Lankford, and J. Linden Adenosine A2A receptor activation reduces infarct size in the isolated, perfused mouse heart by inhibiting resident cardiac mast cell degranulation Am J Physiol Heart Circ Physiol, November 1, 2008; 295(5): H1825 - H1833. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Xi, A. Das, Z.-Q. Zhao, V. F. Merino, M. Bader, and R. C. Kukreja Loss of Myocardial Ischemic Postconditioning in Adenosine A1 and Bradykinin B2 Receptors Gene Knockout Mice Circulation, September 30, 2008; 118(14_suppl_1): S32 - S37. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Murphy and C. Steenbergen Mechanisms Underlying Acute Protection From Cardiac Ischemia-Reperfusion Injury Physiol Rev, April 1, 2008; 88(2): 581 - 609. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
