The adenosine A1 receptor agonist CHA significantly reduced myocardial infarct size to 30% compared to 52% in control wild-type hearts, but failed to exert cardioprotection in A2A or A2B knockout mice.
Does the adenosine A1 receptor agonist CHA improve postischemic left ventricular developed pressure and reduce infarct size in isolated perfused mouse hearts, and is this dependent on A2A and A2B receptors?
Adenosine A1 receptor-mediated cardioprotection requires the presence of both A2A and A2B receptors, indicating complex interactions among adenosine receptor subtypes in ischemia-reperfusion injury.
Absolute Event Rate: 30% vs 52%
p-value: p=<0.05
All four adenosine receptor subtypes have been shown to play a role in cardioprotection, and there is evidence that all four subtypes may be expressed in cardiomyocytes. There is also increasing evidence that optimal adenosine cardioprotection requires the activation of more than one receptor subtype. The purpose of this study was to determine whether adenosine A(2A) and/or A(2B) receptors modulate adenosine A(1) receptor-mediated cardioprotection. Isolated perfused hearts of wild-type (WT), A(2A) knockout (KO), and A(2B)KO mice, perfused at constant pressure and constant heart rate, underwent 30 min of global ischemia and 60 min of reperfusion. The adenosine A(1) receptor agonist N(6)-cyclohexyladenosine (CHA; 200 nM) was administrated 10 min before ischemia and for the first 10 min of reperfusion. Treatment with CHA significantly improved postischemic left ventricular developed pressure (74 ± 4% vs. 44 ± 4% of preischemic left ventricular developed pressure at 60 min of reperfusion) and reduced infarct size (30 ± 2% with CHA vs. 52 ± 5% in control) in WT hearts, effects that were blocked by the A(1) antagonist 8-cyclopentyl-1,3-dipropylxanthine (100 nM). Treatments with the A(2A) receptor agonist CGS-21680 (200 nM) and the A(2B) agonist BAY 60-6583 (200 nM) did not exert any beneficial effects. Deletion of adenosine A(2A) or A(2B) receptor subtypes did not alter ischemia-reperfusion injury, but CHA failed to exert a cardioprotective effect in hearts of mice from either KO group. These findings indicate that both adenosine A(2A) and A(2B) receptors are required for adenosine A(1) receptor-mediated cardioprotection, implicating a role for interactions among receptor subtypes.
Zhan et al. (Sat,) conducted a other in Myocardial ischemia-reperfusion injury. N6-cyclohexyladenosine (CHA) vs. Control (vehicle) was evaluated on Infarct size as a percentage of the total left ventricle (p=<0.05). The adenosine A1 receptor agonist CHA significantly reduced myocardial infarct size to 30% compared to 52% in control wild-type hearts, but failed to exert cardioprotection in A2A or A2B knockout mice.