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The renin–angiotensin system in cardiovascular autonomic control: recent developments and clinical implications

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Abstract

Complex and bidirectional interactions between the renin–angiotensin system (RAS) and autonomic nervous system have been well established for cardiovascular regulation under both physiological and pathophysiological conditions. Most research to date has focused on deleterious effects of components of the vasoconstrictor arm of the RAS on cardiovascular autonomic control, such as renin, angiotensin II, and aldosterone. The recent discovery of prorenin and the prorenin receptor have further increased our understanding of RAS interactions in autonomic brain regions. Therapies targeting these RAS components, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers, are commonly used for treatment of hypertension and cardiovascular diseases, with blood pressure-lowering effects attributed in part to sympathetic inhibition and parasympathetic facilitation. In addition, a vasodilatory arm of the RAS has emerged that includes angiotensin-(1–7), ACE2, and alamandine, and promotes beneficial effects on blood pressure in part by reducing sympathetic activity and improving arterial baroreceptor reflex function in animal models. The role of the vasodilatory arm of the RAS in cardiovascular autonomic regulation in clinical populations, however, has yet to be determined. This review will summarize recent developments in autonomic mechanisms involved in the effects of the RAS on cardiovascular regulation, with a focus on newly discovered pathways and therapeutic targets for this hormone system.

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Abbreviations

Ang:

Angiotensin

ACE:

Angiotensin-converting enzyme

AT1 :

Angiotensin type 1

ARBs:

Angiotensin receptor blockers

AT2 :

Angiotensin type 2

ARC:

Arcuate nucleus

CVLM:

Caudal ventrolateral medulla

MrgD:

Mas-related G-protein coupled receptor D

MR:

Mineralocorticoid receptors

NEP:

Neutral endopeptidase

OVLT:

Organum vasculosum of the lamina terminalis

PRR:

Prorenin receptor

PVN:

Paraventricular nucleus

RAS:

Renin–angiotensin system

RVLM:

Rostral ventrolateral medulla

NTS:

Nucleus tractus solitarius [solitary tract nucleus]

SFO:

Subfornical organ

SNS:

Sympathetic nervous system

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Acknowledgements

ACA is supported by NIH grants R00HL122507 and UL1TR002014. AJM is supported by American Heart Association grant 18POST33960087.

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  1. Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, 500 University Drive, Mail Code H109, Hershey, PA, 17033, USA

    Amanda J. Miller & Amy C. Arnold

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  1. Amanda J. Miller
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Correspondence to Amy C. Arnold.

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Miller, A.J., Arnold, A.C. The renin–angiotensin system in cardiovascular autonomic control: recent developments and clinical implications. Clin Auton Res 29, 231–243 (2019). https://doi.org/10.1007/s10286-018-0572-5

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  • DOI: https://doi.org/10.1007/s10286-018-0572-5

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