Chronic low-level vagus nerve stimulation improves long-term survival in salt-sensitive hypertensive rats

Elizabeth M. Annoni, Dusty Van Helden, Yugene Guo, Brett Levac, Imad Libbus, Bruce H. KenKnight, John W. Osborn, Elena G. Tolkacheva

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3 Scopus citations


Chronic hypertension (HTN) affects more than 1 billion people worldwide, and is associated with an increased risk of cardiovascular disease. Despite decades of promising research, effective treatment of HTN remains challenging. This work investigates vagus nerve stimulation (VNS) as a novel, device-based therapy for HTN treatment, and specifically evaluates its effects on long-term survival and HTN-associated adverse effects. HTN was induced in Dahl salt-sensitive rats using a high-salt diet, and the rats were randomly divided into two groups: VNS (n = 9) and Sham (n = 8), which were implanted with functional or non-functional VNS stimulators, respectively. Acute and chronic effects of VNS therapy were evaluated through continuous monitoring of blood pressure (BP) and ECG via telemetry devices. Autonomic tone was quantified using heart rate (HR), HR variability (HRV) and baroreflex sensitivity (BRS) analysis. Structural cardiac changes were quantified through gross morphology and histology studies. VNS significantly improved the long-term survival of hypertensive rats, increasing median event-free survival by 78% in comparison to Sham rats. Acutely, VNS improved autonomic balance by significantly increasing HRV during stimulation, which may lead to beneficial chronic effects of VNS therapy. Chronic VNS therapy slowed the progression of HTN through an attenuation of SBP and by preserving HRV. Finally, VNS significantly altered cardiac structure, increasing heart weight, but did not alter the amount of fibrosis in the hypertensive hearts. These results suggest that VNS has the potential to improve outcomes in subjects with severe HTN.

Original languageEnglish (US)
Article number25
JournalFrontiers in Physiology
Issue numberJAN
StatePublished - 2019

Bibliographical note

Funding Information:
This study was partially supported by the National Science Foundation grants CAREER PHY-125541, DCSD 1662250 (to ET), National Institutes of Health grant R21HL128790 (to ET), MnDRIVE Neuromodulation Fellowship (to EA), and by LivaNova USA, Inc. [formerly Cyberonics, Inc. (to ET)].

Publisher Copyright:
Copyright © 2019 Annoni, Van Helden, Guo, Levac, Libbus, KenKnight, Osborn and Tolkacheva. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).


  • Autonomic
  • Heart
  • Hypertension
  • Rat
  • Survival
  • Vagus nerve stimulation

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