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

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 XX(th) 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.

Life-threatening events in patients with pheochromocytoma

“…The pathomechanism for this clinical observation remains uncertain; however, there are several hypotheses to explain the hypotensive shock after exposure to high levels of catecholamines. Desensitization of adrenoreceptors, constricted circulatory volume, vasodilatation by abrupt withdrawal of norepinephrine and catecholamine-induced cardiotoxic effects leading to a left ventricular failure have been discussed as possible mechanisms (8,16,17).…”

Adrenaline and Noradrenaline: Partners and Actors in the Same Play"

“…As stated, the fastest cyclization rate occurs in ADR (Bindoli et al, 1992); however, GSH adducts and quinoproteins of ADR have been found in cells, thus showing that ADR quinone can also undergo attack from cellular nucleophiles (Costa et al, 2007, Costa et al, 2009a, Costa et al, 2009c. These changes can ultimately cause cellular injury (Costa et al, 2011).…”

“…Of relevance, the oxidative deamination of catecholamines by MAO leads to another relevant product, hydrogen peroxide (H 2 O 2 ) which subsequently may be converted into the highly reactive hydroxyl radical (HO • ) (Valko et al, 2007), that may cause oxidative stressrelated damage (Carvalho et al, 2001, Duarte et al, 2004, Vaarmann et al, 2010, Costa et al, 2011.…”

“…This indole is often represented as a zwitterionic structure in aqueous solutions (Heacock and Mahon, 1958, Costa et al, 2007 (Figure 5). In summary, the oxidation of catecholamines occurs through two-stages whereby a total of four electrons is removed and an indole is formed by cyclization (Costa et al, 2011). Adrenochrome is the most studied aminochrome due to its stability (Heacock, 1959, Rupp et al, 1994.…”

Oxidative Stress and Drugs of Abuse: An Update

“…The heart is also a target for inflammation induced by drugs of abuse, due to catecholamine release induced by these drugs [169]. The hearts of rats treated with a methamphetamine binge administration regimen presented focal inflammatory infiltrates with abundant monocytes and occasional necrotic foci [170].…”