Our study in rat hearts examined whether activation of adenosine A1 or A3 receptors improved functional recovery and reduced apoptosis resulting from low-flow ischemia. Prior to 30 min low-flow ischemia (0.6 ml/min; 6% of baseline flow), Langendorff rat hearts were preconditioned with two 5-min cycles of (a) ischemia (PC; n=7), (b) infusion of 250 nM adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA; n=6), or (c) infusion of 50 nM adenosine A3 receptor agonist N6-(3-iodobenzyl)-adenosine-5′-N-methyl-uronamide (IB-MECA; n=8). Recovery of function was improved in PC (71±3%), CCPA (68±6%) and IB-MECA (68±4%) groups compared to control hearts (46±5%; P<0.05). Cumulative release of total purines during ischemia-reperfusion was approx. 50% lower in PC, CCPA and IB-MECA groups compared to controls (P<0.05) and was significantly correlated to the percentage functional recovery (R2=0.55; P<0.05). The number of cytosolic histone-associated-DNA fragments, a hallmark of apoptosis and measured by Enzyme Linked ImmunoSorbent Assay (ELISA), was small and not different between groups after 30 min reperfusion. However, CCPA (0.6±0.1 absorbance units) and MECA (0.7±0.1 units; P<0.05 vs. PC) decreased apoptosis after 150 min reperfusion compared to PC (1.4±0.3 units) and control (1.2±0.1 units) hearts. This study shows that adenosine triggers protection of function in preconditioned rat hearts via both the adenosine A1 and A3 receptor. In clinical practice, pharmacological stimulation of adenosine A3 receptors may be advantageous over adenosine A1 receptor activation due to a lack of contractile side-effects. In contrast to ischemic preconditioning, pharmacological stimulation of adenosine A1 or A3 receptors reduced apoptosis. Furthermore, total purine release may serve as a marker of the degree of functional protection.

(Rat), Adenosine A1 receptor, Adenosine A3 receptor, Apoptosis, Ischemia, Ischemic preconditioning
dx.doi.org/10.1016/S0014-2999(01)01611-9, hdl.handle.net/1765/62550
European Journal of Pharmacology
Department of Cardiology

de Jonge, R, Out, M, Maas, W.J, & de Jong, J.W. (2002). Preconditioning of rat hearts by adenosine A1 or A3 receptor activation. European Journal of Pharmacology, 441(3), 165–172. doi:10.1016/S0014-2999(01)01611-9