Premium
Differential effects of adenosine A2A and A2B receptors on basal coronary regulation and ischemia‐induced hyperemia
Author(s) -
Tan Xinglin,
Cai Chun,
Tilley Stephen L,
Ledent Catherine,
Krahn Thomas,
Hofmann Polly A,
Morrison R Ray
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb433
Subject(s) - adenosine , agonist , ischemia , medicine , basal (medicine) , adenosine receptor , chemistry , cardiology , ischemic preconditioning , receptor , endocrinology , insulin
We determined the relative contribution of A 2A and A 2B adenosine receptors (AR) in basal coronary flow (CF), ischemia‐induced coronary hyperemia (CH), and ischemic postconditioning (POC)‐induced coronary protection. Isolated hearts from A 2A AR knockout (A 2A KO) and A 2B KO and their corresponding wild‐type (WT) mice underwent 20 min global ischemia and/or POC with or without pharmacologic analogues of adenosine. Basal CF in A 2A KO but not A 2B KO hearts was lower than that of WT hearts. Inhibition of A 2A AR with 50 nM ZM241385 attenuated basal CF in WT hearts, but inhibition of both A 2A AR and A 2B AR with 500 nM ZM241385 did not further reduce basal CF. Ischemia‐induced CH in A 2B KO but not A 2A KO hearts was lower than that of WT hearts. In WT hearts, CH was reduced by 500 nM but not 50 nM ZM241385. The selective A 2B AR agonist BAY60‐6583 increased CH in A 2A KO hearts, but the selective A 2A AR agonist CGS21680 failed to increase CH in A 2B KO hearts. For all groups, CH induced by 20 min global ischemia was lower than that induced by POC alone, or by 20 min global ischemia followed by POC. Collectively, our data indicate A 2A AR but not A 2B AR is involved in regulating basal CF, while A 2B AR but not A 2A AR is important in ischemia‐induced CH and POC‐mediated coronary protection. (Supported by HL74001 to RRM)