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Angiotensin II, sympathetic nerve activity and chronic heart failure

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Abstract

Sympathetic nerve activity has been reported to be increased in both humans and animals with chronic heart failure. One of the mechanisms believed to be responsible for this phenomenon is increased systemic and cerebral angiotensin II signaling. Plasma angiotensin II is increased in humans and animals with chronic heart failure. The increase in angiotensin II signaling enhances sympathetic nerve activity through actions on both central and peripheral sites during chronic heart failure. Angiotensin II signaling is enhanced in different brain sites such as the paraventricular nucleus, the rostral ventrolateral medulla and the area postrema. Blocking angiotensin II type 1 receptors decreases sympathetic nerve activity and cardiac sympathetic afferent reflex when therapy is administered to the paraventricular nucleus. Injection of an angiotensin receptor blocker into the area postrema activates the sympathoinhibitory baroreflex. In peripheral regions, angiotensin II elevates both norepinephrine release and synthesis and inhibits norepinephrine uptake at nerve endings, which may contribute to the increase in sympathetic nerve activity seen in chronic heart failure. Increased circulating angiotensin II during chronic heart failure may enhance the sympathoexcitatory chemoreflex and inhibit the sympathoinhibitory baroreflex. In addition, increased circulating angiotensin II can directly act on the central nervous system via the subfornical organ and the area postrema to increase sympathetic outflow. Inhibition of angiotensin II formation and its type 1 receptor has been shown to have beneficial effects in chronic heart failure patients.

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Abbreviations

ACE:

Angiotensin-converting enzyme

AngII:

Angiotensin II

AT1R:

Angiotensin II type 1 receptor

BP:

Blood pressure

CHF:

Chronic heart failure

CSAR:

Cardiac sympathetic afferent reflex

eNOS:

Endothelial nitric oxide synthase

GABA:

γ-Aminobutyric acid

IML:

Intermediolateral cell column

i.v.:

Intravenous

MAP:

Mean arterial pressure

NE:

Norepinephrine

nNOS:

Neuronal nitric oxide synthase

NOS:

Nitric oxide synthase

NTS:

Nucleus of the solitary tract

PVN:

Paraventricular nucleus

RVLM:

Rostral ventrolateral medulla

SFO:

Subfornical organ

SNA:

Sympathetic nerve activity

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Acknowledgments

This work is funded by grants from the National Health and Medical Research Council (540404, 1021416) and the BUPA Foundation. JG holds a Practitioner Fellowship from the National Health and Medical Research Council, Australia (1019921) and a Senior Clinical Research Fellowship from the Queensland Government. SWS is supported by a NHMRC Training Research Fellowship (1016349).

Conflict of interest

Drs. Yutang Wang, Sai-Wang Seto and Jonathan Golledge have no conflicts of interest or financial ties to disclose.

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  1. The Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University, Townsville, QLD, 4811, Australia

    Yutang Wang, Sai-Wang Seto & Jonathan Golledge

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  1. Yutang Wang
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  2. Sai-Wang Seto
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Correspondence to Jonathan Golledge.

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Wang, Y., Seto, SW. & Golledge, J. Angiotensin II, sympathetic nerve activity and chronic heart failure. Heart Fail Rev 19, 187–198 (2014). https://doi.org/10.1007/s10741-012-9368-1

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