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Conflicting effects of nitric oxide and oxidative stress in chronic heart failure: potential therapeutic strategies

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Abstract

Chronic heart failure (CHF) is characterized by decreased nitric oxide (NO) bioavailability. In addition, the beneficial NO turns to be deleterious when it reacts with superoxide anion, leading to peroxynitrite formation. Numerous experimental and clinical studies have reported increased production of reactive oxygen species (superoxide, hydrogen peroxide, hydroxyl radical) both in animals and patients with CHF. Moreover, there are indicative data suggesting mechanisms associated with endothelial dysfunction in states of CHF, mainly attributed to decreased NO bioavailability and enhanced inactivation of the latter. Thus, such molecules appear to be potential targets in patients with CHF. These patients are strong candidates to receive a variety of therapeutic agents, some of which have known antioxidant effects. Classic treatment with statins or angiotensin converting enzyme inhibitors has been found to be beneficial in restoring NO and improving myocardial function and structure. Other agents such as sildenafil and b-blockers along with novel agents such as NO synthase transcription enhancers have been proved to be also beneficial, but their use for such a purpose is still controversial. Approaches using more-effective antioxidants or targeting myocardial oxidant-producing enzymes and oxidative or nitrosative stress might be promising strategies in the future.

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  1. 1st Cardiology Unit, Athens University Medical School, Athens, Greece

    Dimitris Tousoulis, Nikolaos Papageorgiou, Alexandros Briasoulis, Emmanouel Androulakis, Marietta Charakida, Eleftherios Tsiamis & Christodoulos Stefanadis

  2. Hippokration Hospital, Athens University Medical School, Vasilissis Sofias 114, 115 28, Athens, Greece

    Dimitris Tousoulis

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  1. Dimitris Tousoulis
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Dimitris Tousoulis and Nikolaos Papageorgiou have equally contributed.

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Tousoulis, D., Papageorgiou, N., Briasoulis, A. et al. Conflicting effects of nitric oxide and oxidative stress in chronic heart failure: potential therapeutic strategies. Heart Fail Rev 17, 65–79 (2012). https://doi.org/10.1007/s10741-011-9228-4

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