Contribution of Catecholamine Reactive Intermediates and Oxidative Stress to the Pathologic Features of Heart Diseases

V.      M. Costa; F.      Carvalho; M.      L. Bastos; R.      A. Carvalho; M.      Carvalho; F.      Remiao

Abstract

Pathologic heart conditions, particularly heart failure (HF) and ischemia-reperfusion (I/R) injury, are characterized by sustained elevation of plasma and interstitial catecholamine levels, as well as by the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Despite the continuous and extensive research on catecholamines since the early years of the XXth century, the mechanisms underlying catecholamine-induced cardiotoxicity are still not fully elucidated. The role of catecholamines in HF, stress cardiomyopathy, I/R injury, ageing, stress, and pheochromocytoma will be thoroughly discussed. Furthermore and although the noxious effects resulting from catecholamine excess have traditionally been linked to adrenoceptors, in fact, several evidences indicate that oxidative stress and the oxidation of catecholamines can have important roles in catecholamine-induced cardiotoxicity. Accordingly, the reactive intermediates formed during catecholamine oxidation have been associated with cardiac toxicity, both in in vitro and in vivo studies. An insight into the influence of ROS, RNS, and catecholamine oxidation products on several heart diseases and their clinical course will be provided. In addition, the source and type of oxidant species formed in some heart pathologies will be referred. In this review a special focus will be given to the research of cardiac pathologies where catecholamines and oxidative stress are involved. An integrated vision of these matters is required and will be provided along this review, namely how the concomitant surge of catecholamines and ROS occurs and how they can be interconnected. The concomitant presence of these factors can elicit peculiar and not fully characterized responses on the heart. We will approach the existing data with new perspectives as they can help explaining several controversial results regarding cardiovascular diseases and the redox ability of catecholamines.

Keywords: Catecholamines, oxidative stress, cardiovascular toxicity, Pathologic heart conditions, heart failure, HF, ischemia-reperfusion, interstitial catecholamine levels, ROS, RNS