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Selective adenosine A3 receptor stimulation reduces ischemic myocardial injury in the rabbit heart.

AbstractOBJECTIVE:
The aim of this study was to determine whether selective activation of the adenosine A3 receptor reduces infarct size in a Langendorff model of myocardial ischemia-reperfusion injury.
METHODS:
Buffer-perfused rabbit hearts were exposed to 30 min regional ischemia and 120 min of reperfusion. Infarct size was measured by tetrazolium staining and normalized for area-at-risk (IA/AAR).
RESULTS:
Preconditioning by 5 min global ischemia and 10 min reperfusion reduced infarct size (IA/AAR) to 19 +/- 4% (controls: 67 +/- 5%). Replacing global ischemia with 5 min perfusion of the rabbit A3-selective agonist, IB-MECA (A3 Ki: 2 nM; A1 Ki: 30 nM) elicited a concentration-dependent reduction in infarct size; 50 nM IB-MECA reduced IA/AAR to 24 +/- 4%. The A1-selective agonist, R-PIA (25 nM) reduced IA/AAR to a similar extent (21 +/- 6%). However, while the cardioprotective effect of R-PIA was significantly inhibited (54 +/- 7% IA/AAR) by the rabbit A1-selective antagonist, BWA1433 (50 nM), the IB-MECA-dependent cardioprotection was unaffected (28 +/- 6% IA/AAR). A non-selective (A1 vs. A3) concentration of BWA1433 (5 microM) significantly attenuated the IB-MECA-dependent cardioprotection (61 +/- 7% IA/AAR).
CONCLUSIONS:
These data clearly demonstrate that selective A3 receptor activation provides cardioprotection from ischemia-reperfusion injury in the rabbit heart. Furthermore, the degree of A3-dependent cardioprotection is similar to that provided by A1 receptor stimulation or ischemic preconditioning.
AuthorsW R Tracey, W Magee, H Masamune, S P Kennedy, D R Knight, R A Buchholz, R J Hill
JournalCardiovascular research (Cardiovasc Res) Vol. 33 Issue 2 Pg. 410-5 (Feb 1997) ISSN: 0008-6363 [Print] NETHERLANDS
PMID9074706 (Publication Type: Journal Article)
Chemical References
  • Receptors, Purinergic
  • N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine
  • Phenylisopropyladenosine
  • Adenosine
Topics
  • Adenosine (analogs & derivatives, therapeutic use)
  • Animals
  • Disease Models, Animal
  • Male
  • Myocardial Ischemia (prevention & control)
  • Myocardial Reperfusion Injury (prevention & control)
  • Phenylisopropyladenosine (therapeutic use)
  • Rabbits
  • Receptors, Purinergic (drug effects)
  • Stimulation, Chemical

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