A(1) or A(3) adenosine receptors induce late preconditioning against infarction in conscious rabbits by different mechanisms. Circ Res 2001 Mar 16;88(5):520-8
Date
03/16/2001Pubmed ID
11249876DOI
10.1161/01.res.88.5.520Scopus ID
2-s2.0-0035896182 (requires institutional sign-in at Scopus site) 117 CitationsAbstract
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.
Author List
Takano H, Bolli R, Black RG Jr, Kodani E, Tang XL, Yang Z, Bhattacharya S, Auchampach JAAuthor
John A. Auchampach PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdenineAdenosine
Animals
Binding, Competitive
Cell Line
Consciousness
Decanoic Acids
Humans
Hydroxy Acids
Iodine Radioisotopes
Ischemic Preconditioning, Myocardial
Membranes
Myocardial Infarction
Nitroarginine
Norbornanes
Phenethylamines
Rabbits
Radioligand Assay
Receptor, Adenosine A3
Receptors, Purinergic P1