A1 or A3 adenosine receptors induce late preconditioning against infarction in conscious rabbits by different mechanisms

Hitoshi Takano, Roberto Bolli, Richard G. Black, Eitaro Kodani, Xian Liang Tang, Zequan Yang, Samita Bhattacharya, John A. Auchampach

Research output: Contribution to journalArticlepeer-review

Abstract

We investigated whether activation of A1 or A3 adenosine receptors (ARs) induces late preconditioning (PC) against infarction in conscious rabbits using the selective AR agonists 2-chloro-N6-cyclopentyladenosine (CCPA) and N6-3-iodobenzyladenosine-5′-N-methylcarboxamide (IB-MECA). In vitro radioligand binding and cAMP assays demonstrated CCPA to be ≈200- to 400-fold selective for the rabbit A1AR and IB-MECA to be ≈20-fold selective for the rabbit A3AR. We observed that (1) pretreatment of rabbits 24 hours earlier with CCPA (100 μg/kg IV bolus) or IB-MECA (100 or 300 μg/kg) resulted in an ≈35% to 40% reduction in the size of the infarct induced by 30 minutes of coronary artery occlusion and 72 hours of reperfusion compared with vehicle-treated rabbits, whereas pretreatment with the selective A2AAR agonist CGS 21680 (100 μg/kg) had no effect; (2) the delayed cardioprotective effect of CCPA, but not that of IB-MECA, was completely blocked by coadministration of the highly selective A1AR antagonist N-0861; (3) inhibition of nitric oxide synthase (NOS) with Nω-nitro-L-arginine during the 30-minute occlusion abrogated the infarct-sparing action of CCPA but not that of IB-MECA; and (4) inhibition of ATP-sensitive potassium (KATP) channels with sodium 5-hydroxydecanoate during the 30-minute occlusion blocked the cardioprotective effects of both CCPA and IB-MECA. Taken together, these results indicate that activation of either A1ARs or A3ARs (but not A2AARs) elicits delayed protection against infarction in conscious rabbits and that both A1AR- and A3AR-induced cardioprotection involves opening of KATP channels. However, A1AR-induced late PC uses an NOS-dependent pathway whereas A3AR-induced late PC is mediated by an NOS-independent pathway.

Original languageEnglish (US)
Pages (from-to)520-528
Number of pages9
JournalCirculation research
Volume88
Issue number5
DOIs
StatePublished - Mar 16 2001

Keywords

  • ATP-dependent potassium channels
  • Adenosine receptors
  • Ischemia/reperfusion injury
  • Myocardial infarction
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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