The Role of the Beta-Adrenergic Signal Transduction Pathway in Myocardial Protection

Beta-adrenergic activation is a major factor causing myocardial damage in the context of ischemia. Activation of the beta-adrenergic signal transduction pathway can, however, also elicit protective responses in the myocardium. Activation of the beta-adrenergic signal transduction pathway participates in the protective effect of ischemic preconditioning, and administration of catecholaminergic agents such as isoproterenol and noradrenaline can elicit pharmacological preconditioning. Protection induced by beta-adrenergic activation (beta-adrenergic preconditioning) elicits both classic (early) and delayed (late) preconditioning and utilizes adenosine to mediate acute protection, while utilizing NO in pharmacological late beta-preconditioning. It is unclear which beta-adrenergic receptor subtype is involved in mediating protection, with evidence for a role of both the “harmful” receptor, beta1, and the beta2 adrenergic receptor. Our own findings suggest cAMP and PKA as the second messengers involved in this ability of beta-adrenergic activation to activate a protective response during the triggering phase of protection, whereas attenuation of activation of p38 MAPK during ischemia is involved in protection against ischemia-mediated necrosis and apoptosis.