A1 ADENOSINE RECEPTOR AND MITOCHONDRIA: TARGETS OF REMOTE ISCHEMIC PRECONDITIONING

PAEZ D; GARCES M; CALABRO V; BIN EP; DANNUNZIO V; DEL MAURO J; MARCHINI T; HOCHT C; EVELSON P; GELPI RJ; DONATO M

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY

AMER PHYSIOLOGICAL SOC

Lugar: Bethesda; Año: 2019

0363-6135

Adenosine is involved in classic preconditioning in most species and acts especially through adenosine A1 and A3 receptors. The aim of our study was to evaluate whether remote ischemic preconditioning (rIPC) activates A1 adenosine receptors and improves mitochondrial function, thereby reducing myocardial infarct size. 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, a rIPC protocol (3 cycles of hindlimb ischemia/reperfusion) was performed. The infarct size was measured with tetrazolium staining, and Akt/eNOS expression/phosphorylation and mitochondrial function were evaluated after ischemia at 10 and 60 min of reperfusion. As expected, rIPC significantly decreased the infarct size. This beneficial effect was only abolished when DPCPX (A1 receptor blocker) and L-NAME (NO synthesis inhibitor) were administered during the reperfusion phase. At the early reperfusion phase, rIPC induced significant Akt and eNOS phosphorylation, which was abolished by the perfusion with an A1 receptor blocker. I/R lead to impaired mitochondrial function, which was attenuated by rIPC and mediated by A1 adenosine receptors. In conclusion, we demonstrated that rIPC limits myocardial infarct by activation of A1 adenosine receptor at early reperfusion in the isolated rat heart. Interestingly, rIPC appears to reduce myocardial infarct size by Akt/eNOS pathway and improving mitochondrial function during myocardial reperfusion.