Oxidative stress and heart failure

Abstract

Various abnormalities have been implicated in the transition of hypertrophy to heart failure but the exact mechanism is still unknown. Thus heart failure subsequent to hypertrophy remains a major clinical problem. Recently, oxidative stress has been suggested to play a critical role in the pathogenesis of heart failure. Here we describe antioxidant changes as well as their significance during hypertrophy and heart failure stages. Heart hypertrophy in rats and guinea pigs, in response to pressure overload, is associated with an increase in 'antioxidant reserve' and a decrease in oxidative stress. Hypertrophied rat hearts show increased tolerance for different oxidative stress conditions such as those imposed by free radicals, hypoxia-reoxygenation and ischemia-reperfusion. On the other hand, heart failure under acute as well as chronic conditions is associated with reduced antioxidant reserve and increased oxidative stress. The latter may have a causal role as suggested by the protection seen with antioxidant treatment in acute as well as in chronic heart failure. It is becoming increasingly apparent that, anytime the available antioxidant reserve in the cell becomes inadequate, myocardial dysfunction is imminent.

Increased Gene Expression of Glutathione Peroxidase-3 in Diabetic Mouse Heart

“…Among these genes, we focused on an antioxidant enzyme, GPX-3, since augmented oxidative stress is implicated in the pathogenesis of cardiac dysfunction. [7][8][9] Increased Expression of the GPX-3 Gene in the Heart under Hyperglycemia To confirm the augmented expression of GPX-3 gene in the diabetic mouse heart, northern blot analyses were carried out using total RNA isolated from STZ-induced diabetic mice. As shown in Fig.…”

“…12) Furthermore, increasing evidence suggests that oxidative stress also plays a critical role in the pathogenesis of heart failure. [7][8][9] It can therefore be postulated that augmented oxidative stress under hyperglycemia may accelerate the development of heart failure in diabetic patients.…”

Positive inotropic and lusitropic effects of HNO/NO − in failing hearts: Independence from β-adrenergic signaling

“…This has been revealed indirectly by showing enhanced dobutamine or isoproterenol-stimulated function in mice lacking the endothelial NO synthase gene (18,19) or in control animals and humans after NO synthase inhibition (5,9,20). Importantly, this negative interaction appears enhanced in failing myocardium, which has been attributed to altered inducible NO synthase activity (21), down-regulated cGMP catabolism (22), enhanced ␤ 3 -receptor signaling (23,24), and enhanced oxidant stress (25)(26)(27). ␤-Adrenergic stimulation further increases NO release (28) and can amplify its depressant modulation.…”

DietaryL-Cysteine Improves the Antioxidative Potential and Lipid Metabolism in Rats Fed a Normal Diet

“…[1][2][3] Various antioxidative enzymes and non-enzymatic antioxidants protect DNA against strand breaks and cells against oxidative damage as a way to scavenge reactive oxygen species (ROS) and free radicals. 4) These include catalase, superoxide dismutase, glutathione peroxidase (GPx), glutathione (GSH), vitamin E, uric acid, and sulfhydryl amino acid.…”