Preconditioning of rat hearts by adenosine A1 or A3 receptor activation

Abstract Our study in rat hearts examined whether activation of adenosine A 1 or A 3 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 A 1 receptor agonist 2-chloro- N 6 -cyclopentyladenosine (CCPA; n =6), or (c) infusion of 50 nM adenosine A 3 receptor agonist N 6 -(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 P R 2 =0.55; P P 1 and A 3 receptor. In clinical practice, pharmacological stimulation of adenosine A 3 receptors may be advantageous over adenosine A 1 receptor activation due to a lack of contractile side-effects. In contrast to ischemic preconditioning, pharmacological stimulation of adenosine A 1 or A 3 receptors reduced apoptosis. Furthermore, total purine release may serve as a marker of the degree of functional protection.