Ischemic Preconditioning and the β-Adrenergic Signal Transduction Pathway

Background—Previous studies from our laboratory showed cyclic increases in tissue cAMP during a multiple-cycle preconditioning (PC) protocol, followed by attenuated cAMP accumulation during sustained ischemia. The aim of this study was to determine whether ischemia-induced activation of the β-adrenergic signaling pathway could act as a trigger in eliciting protection. Methods and Results—Isolated perfused rat hearts were preconditioned by 3×5 minutes of global ischemia, interspersed by 5 minutes of reperfusion. β-Adrenergic responsivity was assessed by measurement of tissue cAMP generation after β-adrenergic agonist administration at the end of the PC protocol. Tissue cAMP, adenylyl cyclase, and protein kinase A (PKA) activities and β-adrenergic receptor characteristics were assessed at different times. The role of cAMP generation in eliciting PC was studied by investigation of functional recovery during reperfusion after 25 minutes of global ischemia after (1) cAMP increases in the trigger period were pr...