Modulation of Sympathetic Overactivity to Treat Resistant Hypertension

  • Raven VooraEmail author
  • Alan L. Hinderliter
Mechanisms of Hypertension (M Weir, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Mechanisms of Hypertension


Purpose of Review

To review the role and evidence for sympathetic overactivity in resistant hypertension and review the therapies that have been studied to modulate the sympathetic nervous system to treat resistant hypertension, with a focus on non-pharmacologic therapies such as renal denervation, baroreflex activation therapy, and carotid body ablation.

Recent Findings

Based on the two best current techniques available for assessing sympathetic nerve activity, resistant hypertension is characterized by increased sympathetic nerve activity. Several device therapies, including renal denervation baroreflex activation therapy and carotid body ablation, have been developed as non-pharmacologic means of reducing blood pressure in resistant hypertension. With respect to renal denervation, the technologies for renal denervation have evolved since the unfavorable results from the HTN-3 study, and the revised technologies are being actively studied. Data from the first phase of the SPYRAL HTN Clinical Trial Program have been published. Results from the SPYRAL HTN-OFF MED trial suggest that ablating renal nerves can reduce blood pressure in patients with untreated mild-to-moderate hypertension. The SPYRAL HTN-ON MED trial demonstrated the safety and efficacy of catheter-based renal denervation in patients with uncontrolled hypertension on antihypertensive treatment. Interestingly, there was a high rate of medication non-adherence among patients with hypertension in this study. One attractive alternative to radiofrequency ablation is the use of ultrasound for renal denervation. Proof of concept data for the Paradise endovascular ultrasound renal denervation system was recently published in the RADIANCE-HTN SOLO trial. The results of this trial indicate that, among patients with mild to moderate hypertension on no medications, renal denervation with the Paradise system results in a greater reduction in both SBP and DBP at 2months compared with a sham procedure. Overall reductions were similar in magnitude to those noted in the SPYRAL HTN-OFF MED study. With respect to carotid body ablation, there is an ongoing proof of concept study that is investigating the safety and feasibility of ultrasound-based endovascular carotid body ablation in 30 subjects with treatment-resistant hypertension outside of the USA.


The sympathetic nervous system is an important contributor to resistant hypertension. Modulation of sympathetic overactivity should be an important goal of treatment. Innovative therapies using non-pharmacologic means to suppress the sympathetic nervous system are actively being studied to treat resistant hypertension.


Resistant hypertension Sympathetic nervous system Renal denervation 


Compliance with Ethical Standards

Conflict of Interest

Dr. Hinderliter receives grant support from ReCor Medical for participation in the RADIANCE-HTN trial. Dr. Voora declares no conflicts of interest relevant to this manuscript.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Medicine, Division of Nephrology and HypertensionUniversity of North CarolinaChapel HillUSA
  2. 2.Department of Medicine, Division of CardiologyUniversity of North CarolinaChapel HillUSA

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