Role of A1 adenosine receptor in remote ischemic preconditioning mechanism

BIN, ELIANA; MARCHINI, TIMOTEO; GELPI, RICARDO J; PAEZ, DIAMELA; DEL MAURO, JULIETA; EVELSON, PABLO; GARCÉS, MARIANA; HÖCHT, CHRISTIAN; DONATO, MARTÍN

Buenos Aires

Congreso; IV International Congress in Translational Medicine; 2018

International Master Program in Biomedical Sciences (IMBS)

Background: Adenosine is involved in classic preconditioning in most species and acts especially through adenosine A1 and A3 receptors. However, the role of this nucleoside in hearts subjected to remote ischemic preconditioning (rIPC) has been poorly studied. Objetive: The objective of our study was evaluate whether remote rIPC activates the A1 adenosine receptors and improves mitochondrial function, thereby reducing myocardial infarct size. Methods: Isolated rat hearts were subjected to 30 min of global ischemia and 60 min of reperfusion (I/R). In a second group, before isolation of the heart, rIPC protocol (3 cycles of indlimb ischemia/reperfusion) was performed. Additionally, two experimental groups were studied, in which a DPCPX (adenosine A1 blocker) or L-NAME (NO synthesis inhibitor) was administered during first 10 minute of reperfusion. The infarct size was measured with tetrazolium staining and eNOS expression/phosphorylation andmitochondrial function were evaluated after ischemia at 10 and 60 min of reperfusion period Results: As expected, rIPC significantly decreased the infarct size. This beneficial effect was abolished when DPCPX and L-NAME were administered. During the early reperfusion phase, rIPC induced a significant eNOS phosphorylation, which was abolished with the infusion of A1 receptor blocker. I/R lead to an impaired mitochondrial function, which was attenuated by rIPC and mediated by A1 adenosine receptors. Conclusions: We demonstrated in the isolated rat heart that rIPC limits myocardial infarct by activation of A1 adenosine receptor at early reperfusion. Interestingly, rIPC appears to reduce myocardial infarct size by improving mitochondrial function during myocardial reperfusion.