Adenosine A1 Receptor Induced Delayed Preconditioning in Rabbits: Induction of p38 Mitogen-Activated Protein Kinase Activation and Hsp27 Phosphorylation via a Tyrosine Kinase– and Protein Kinase C–Dependent Mechanism

Transient adenosine A1 receptor (A1R) activation in rabbits induces delayed preconditioning against myocardial infarction 24 to 72 hours later. The cellular mechanisms downstream of A1R mediating this delayed cardioprotection have not been elucidated. This study examined the role of protein kinase C (PKC) and tyrosine kinases (TKs) in the signaling cascade mediating A1R-induced late preconditioning in rabbits. The small heat shock protein Hsp27 has been shown to confer cytoskeletal protection when in the phosphorylated state. We therefore also evaluated the potential role of the p38 mitogen-activated protein kinase (p38 MAPK) and Hsp27 as distal mediators of A1R-induced delayed preconditioning. Pharmacological preconditioning of rabbits with the selective A1 agonist 2-chloro-N-cyclopentyladenosine (CCPA; 100 μg/kg) significantly reduced myocardial infarct size compared with control animals, after 30-minute regional ischemia/2-hour reperfusion in vivo 24 hours later (23.7±3.1 versus 43.0±4.1%;P