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Central nervous system circuits modified in heart failure: pathophysiology and therapeutic implications

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Abstract

The pathophysiology of heart failure (HF) is characterized by an abnormal activation of neurohumoral systems, including the sympathetic nervous and the renin–angiotensin–aldosterone systems, which have long-term deleterious effects on the disease progression. Perpetuation of this neurohumoral activation is partially dependent of central nervous system (CNS) pathways, mainly involving the paraventricular nucleus of the hypothalamus and some regions of the brainstem. Modifications in these integrative CNS circuits result in the attenuation of sympathoinhibitory and exacerbation of sympathoexcitatory pathways. In addition to the regulation of sympathetic outflow, these central pathways coordinate a complex network of agents with an established pathophysiological relevance in HF such as angiotensin, aldosterone, and proinflammatory cytokines. Central pathways could be potential targets in HF therapy since the current mainstay of HF pharmacotherapy aims primarily at antagonizing the peripheral mechanisms. Thus, in the present review, we describe the role of CNS pathways in HF pathophysiology and as potential novel therapeutic targets.

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Acknowledgments

This work was supported by the Portuguese Foundation for Science and Technology [Grants PEst-C/SAU/UI0051/2011 and EXCL/BIM-MEC/0055/2012, partially funded by FEDER through COMPETE] through the Cardiovascular R&D Unit and by European Commission [Grant FP7-Health-2010; MEDIA-261409].

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Authors and Affiliations

  1. Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, Alameda Professor Hernâni Monteiro, University of Porto, 4200-319, Porto, Portugal

    Bernardo Sousa-Pinto, Manuel J. Ferreira-Pinto, Mário Santos & Adelino F. Leite-Moreira

  2. Department of Cardiothoracic Surgery, Centro Hospitalar São João, EPE, Porto, Portugal

    Adelino F. Leite-Moreira

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  1. Bernardo Sousa-Pinto
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  2. Manuel J. Ferreira-Pinto
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  3. Mário Santos
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  4. Adelino F. Leite-Moreira
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Correspondence to Adelino F. Leite-Moreira.

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Sousa-Pinto, B., Ferreira-Pinto, M.J., Santos, M. et al. Central nervous system circuits modified in heart failure: pathophysiology and therapeutic implications. Heart Fail Rev 19, 759–779 (2014). https://doi.org/10.1007/s10741-014-9427-x

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