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Local Actions of Natriuretic Peptides and Nitric Oxide in Cardiac Remodeling: Implications for Therapy

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Cardiac Remodeling

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 5))

Abstract

Cardiac remodeling in response to sustained pressure overload involves ­cardiomyocyte hypertrophy and contractile dysfunction together with interstitial changes such as fibrosis and diminished capillary density. These changes are modulated by mechanical forces and factors secreted between and even within cells, exerting paracrine and auto-/intracrine actions. Among these factors are the natriuretic peptides atrial and B-type NPs (ANP and BNP, mainly released from myocytes), C-type NP (CNP, possibly secreted from fibroblasts), as well as nitric oxide (NO) (produced by different myocardial cell types). These factors, which signal through specific guanylyl cyclase receptors and intracellular cyclic GMP as second messenger, may act as key local antihypertrophic, antifibrotic, and proangiogenic factors during cardiac remodeling. This chapter will therefore summarize the insights obtained from experimental and clinical studies to highlight (1) natriuretic peptide- and NO-dependent modulation of myocyte growth and secretion of profibrotic factors, (2) the role of direct fibroblast actions of natriuretic peptides and NO during cardiac hypertrophy, (3) potential local proangiogenic actions of ANP and BNP, (4) alterations of these ligand/receptor systems in cardiac remodeling, and (5) potential therapeutical implications.

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Abbreviations

ANP:

Atrial natriuretic peptide

BNP:

B-type natriuretic peptide

cGKI:

cGMP-dependent protein kinase type I

CNP:

C-type natriuretic peptide

GC:

Guanylyl cyclase receptor

GC:

Guanylyl cyclase

NO:

Nitric oxide

PDE:

Phosphodiesterase

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Acknowledgments

MK’s work reviewed in this chapter was supported by grants from the Deutsche Forschungsgemeinschaft (SFB 688) and from the comprehensive heart failure center (CHFC) in Würzburg. The authors would like to apologize to all colleagues whose studies were not cited for lack of space.

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Authors and Affiliations

  1. Institute of Physiology, University of Würzburg, Röntgenring 9, 97070, Würzburg, Germany

    Michaela Kuhn & Hitoshi Nakagawa

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  1. Michaela Kuhn
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  2. Hitoshi Nakagawa
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Correspondence to Michaela Kuhn .

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Editors and Affiliations

  1. Walter MacKenzie Health Sciences Centre, Division of Cardiology, University of Alberta, 8440-112 Street, Edmonton, T6G 2B7, Alberta, Canada

    Bodh I. Jugdutt

  2. St. Boniface General Hospital Research C, Institute of Cardiovascular Sciences, Tache Avenue 351, Winnipeg, R2H 2A6, Manitoba, Canada

    Naranjan S. Dhalla

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Kuhn, M., Nakagawa, H. (2013). Local Actions of Natriuretic Peptides and Nitric Oxide in Cardiac Remodeling: Implications for Therapy. In: Jugdutt, B., Dhalla, N. (eds) Cardiac Remodeling. Advances in Biochemistry in Health and Disease, vol 5. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5930-9_9

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