A(1) or A(3) adenosine receptors induce late preconditioning against infarction in conscious rabbits by different mechanisms

• Published in: Circulation research Vol. 88; no. 5; pp. 520 - 528
• Main Authors: Takano, H, Bolli, R, Black, Jr, R G, Kodani, E, Tang, X L, Yang, Z, Bhattacharya, S, Auchampach, J A
• Format: Journal Article
• Language: English
• Published: United States Lippincott Williams & Wilkins Ovid Technologies 16.03.2001
• Subjects: Adenine - analogs & derivatives; Adenine - pharmacology; Adenosine - analogs & derivatives; Adenosine - metabolism; Adenosine - pharmacology; Animals; Binding, Competitive - drug effects; Cell Line; Consciousness; Decanoic Acids - pharmacology; Humans; Hydroxy Acids - pharmacology; Iodine Radioisotopes; Ischemic Preconditioning, Myocardial; Membranes - metabolism; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; Myocardial Infarction - prevention & control; Nitroarginine - pharmacology; Norbornanes - pharmacology; Phenethylamines - pharmacology; Rabbits; Radioligand Assay; Receptor, Adenosine A3; Receptors, Purinergic P1 - drug effects; Receptors, Purinergic P1 - genetics; Receptors, Purinergic P1 - metabolism
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.RES.88.5.520

We investigated whether activation of A(1) or A(3) adenosine receptors (ARs) induces late preconditioning (PC) against infarction in conscious rabbits using the selective AR agonists 2-chloro-N(6)-cyclopentyladenosine (CCPA) and N(6)-3-iodobenzyladenosine-5'-N-methylcarboxamide (IB-MECA). In vitro radioligand binding and cAMP assays demonstrated CCPA to be approximately 200- to 400-fold selective for the rabbit A(1)AR and IB-MECA to be approximately 20-fold selective for the rabbit A(3)AR. We observed that (1) pretreatment of rabbits 24 hours earlier with CCPA (100 microgram/kg IV bolus) or IB-MECA (100 or 300 microgram/kg) resulted in an approximately 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 A(2A)AR agonist CGS 21680 (100 microgram/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 A(1)AR antagonist N-0861; (3) inhibition of nitric oxide synthase (NOS) with N(omega)-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 (K(ATP)) 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 A(1)ARs or A(3)ARs (but not A(2A)ARs) elicits delayed protection against infarction in conscious rabbits and that both A(1)AR- and A(3)AR-induced cardioprotection involves opening of K(ATP) channels. However, A(1)AR-induced late PC uses an NOS-dependent pathway whereas A(3)AR-induced late PC is mediated by an NOS-independent pathway.