Clinical Autonomic Research

, Volume 29, Issue 2, pp 231–243 | Cite as

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

  • Amanda J. Miller
  • Amy C. ArnoldEmail author
Review Article


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.


Renin–angiotensin system Autonomic nervous system Blood pressure Baroreflex 





Angiotensin-converting enzyme


Angiotensin type 1


Angiotensin receptor blockers


Angiotensin type 2


Arcuate nucleus


Caudal ventrolateral medulla


Mas-related G-protein coupled receptor D


Mineralocorticoid receptors


Neutral endopeptidase


Organum vasculosum of the lamina terminalis


Prorenin receptor


Paraventricular nucleus


Renin–angiotensin system


Rostral ventrolateral medulla


Nucleus tractus solitarius [solitary tract nucleus]


Subfornical organ


Sympathetic nervous system



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

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Neural and Behavioral SciencesPennsylvania State University College of MedicineHersheyUSA

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