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  • Review Article
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Natriuretic peptides in cardiometabolic regulation and disease

Nature Reviews Cardiology volume 11, pages 403–412 (2014)Cite this article

Subjects

Key Points

  • Identification of natriuretic peptide receptors in a broad range of tissues, including the pancreas, liver, and adipose tissues, implies biological effects beyond pressure–volume homeostasis

  • In population-based studies, low circulating concentrations of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are associated with obesity and metabolic dysfunction

  • Genetically determined increased concentrations of ANP and BNP are associated with reduced blood pressure and reduced risk of hypertension in animal models and in the general population

  • Natriuretic peptides are implicated in endogenous protection against atherosclerosis, thrombosis, myocardial ischaemia, and cardiac remodelling in experimental animal models, and large-scale clinical studies evaluating their infarct-sparing effects are in progress

  • Dysregulation of the natriuretic peptides might be important in the initiation of metabolic dysfunction and could lead to cardiovascular complications, such as atherosclerosis, thrombosis, hypertension, and myocardial ischaemia

Abstract

In the 30 years since the identification of the natriuretic peptides, their involvement in regulating fluid and blood pressure has become firmly established. Data indicating a role for these hormones in lifestyle-related metabolic and cardiovascular disorders have also accumulated over the past decade. Dysregulation of the natriuretic peptide system has been associated with obesity, glucose intolerance, type 2 diabetes mellitus, and essential hypertension. Moreover, the natriuretic peptides have been implicated in the protection against atherosclerosis, thrombosis, and myocardial ischaemia. All these conditions can coexist and potentially lead to heart failure, a syndrome associated with a functional natriuretic peptide deficiency despite high circulating concentrations of immunoreactive peptides. Therefore, dysregulation of the natriuretic peptide system, a 'natriuretic handicap', might be an important factor in the initiation and progression of metabolic dysfunction and its accompanying cardiovascular complications. This Review provides a summary of the natriuretic peptide system and its involvement in these cardiometabolic conditions. We propose that these peptides might have an integrating role in lifestyle-related metabolic and cardiovascular disorders.

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Figure 1: The natriuretic peptides exert their effects through transmembrane receptors: NPR-A, NPR-B, and NPR-C.
Figure 2: Within adipocytes, adrenergic stimulation through the β-AR stimulates lipolysis as well as a phenotypic change into a brown-like adipocyte with increased thermogenic capacity.

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Acknowledgements

N.E.Z. and J.P.G. are supported by unrestricted grants from Novo Nordisk A/S and the Research Council at Copenhagen University Hospital, Rigshospitalet, Denmark. The funding had no role in the present manuscript and only supported a postdoctoral salary for N.E.Z.

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, Copenhagen, DK-2100, Denmark

    Nora E. Zois, Emil D. Bartels, Ingrid Hunter & Jens P. Goetze

  2. Department of Clinical Medicine, Faculty of Health Sciences, Aarhus University, Brendstrupgaardsvej 100, Aarhus, DK-8200, Denmark

    Birgitte S. Kousholt

  3. Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, Copenhagen, DK-1870, Denmark

    Lisbeth H. Olsen

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All the authors researched data, contributed to the discussion of content, and reviewed/edited the article before submission. The manuscript was written by N.E.Z. and J.P.G.

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Zois, N., Bartels, E., Hunter, I. et al. Natriuretic peptides in cardiometabolic regulation and disease. Nat Rev Cardiol 11, 403–412 (2014). https://doi.org/10.1038/nrcardio.2014.64

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