NADPH oxidase-derived superoxide impairs calcium transients and contraction in aged murine ventricular myocytes

Abstract

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Swimming exercise reverses aging-related contractile abnormalities of female heart by improving structural alterations

“…In aging hearts, however, decreased Ca 2+ removal rate and altered Ca 2+ handling which precede slowed contraction may eventually result in ventricular dysfunction [1]. Despite this hypothesis, somewhat unchanged [3], depressed [4,5] or increased [6] results have been reported for cell shortening and Ca 2+ transient amplitude in animal models of senescent heart. The most likely mechanisms that account for these alterations in cardiac excitation-contraction (E-C) coupling are L-type Ca 2+ current (I CaL ) and altered activity or expression of Ca 2+ regulatory proteins which may lead to impaired SR function.…”

“…Ca 2+ handling alterations due to changes in the expression and/or function of Ca 2+ regulatory proteins may also contribute to functional abnormalities observed in myocytes from aged hearts [1,6,16]. Accordingly, training dependent enhancement in systolic function of the aging heart has been ascribed to the improvement in Ca 2+ handling of ventricular myocytes [15,19].…”

“…Of the NOXs currently known, NOX-4 has been suggested to drive oxidative stress in the mitochondria either alone or by stimulating ROS-induced ROS release, thereby exacerbating mitochondrial dysfunction which may result in cardiac dysfunction [13]. Recently, one study showing augmented NOX-4 expression in aged myocytes has gone further to propose a causal link between NOX--derived oxidative stress and decelerated contraction kinetics of cardiac myocytes from aged mice [6]. Consistently, in our study, NOX-4 was significantly increased in aged hearts but exercise training did not change the elevated level of NOX-4.…”

“…However, the upregulation of GSH in exercised rats may protect the macromolecules against oxidative damage and reverses the structural abnormalities of myocardium in aged heart. As a consequence, swimming exercise stimulates the upregulation of antioxidant enzyme activity which counteracts the detrimental effects of ROS in myocardium and thereby improves the contractile function [6].…”

“…Reactive oxygen species, accumulation of which has been substantially accentuated with advanced age, can also lead to functional abnormalities [6]. Due to its high metabolic demand, heart is rich in mitochondria, and therefore susceptible to oxidative damage [22].…”