Abstract
SIGNIFICANCE: Heart failure (HF) results from poor heart function and is the leading cause of death in Western society. Abnormalities of Ca(2+) handling at the level of the ventricular myocyte are largely responsible for much of the poor heart function. RECENT ADVANCES: Although studies have unraveled numerous mechanisms for the abnormal Ca(2+) handling, investigations over the past decade have indicated that much of the contractile dysfunction and adverse remodeling that occurs in HF involves oxidative stress. CRITICAL ISSUES: Regrettably, antioxidant therapy has been an immense disappointment in clinical trials. Thus, redox signaling is being reassessed to elucidate why antioxidants failed to treat HF. FUTURE DIRECTIONS: A recently identified aspect of redox signaling (specifically the superoxide anion radical) is its interaction with nitric oxide, known as the nitroso-redox balance. There is a large nitroso-redox imbalance with HF, and we suggest that correcting this imbalance may be able to restore myocyte contraction and improve heart function.