Neurohormones in the Pathophysiology of Vasovagal Syncope in Adults

David G. Benditt, J. Gert van Dijk, Darshan Krishnappa, Wayne O. Adkisson, Scott Sakaguchi

Research output: Contribution to journalReview articlepeer-review

18 Scopus citations


Vasovagal syncope (VVS) is the most common cause of syncope across all age groups. Nonetheless, despite its clinical importance and considerable research effort over many years, the pathophysiology of VVS remains incompletely understood. In this regard, numerous studies have been undertaken in an attempt to improve insight into the evolution of VVS episodes and many of these studies have examined neurohormonal changes that occur during the progression of VVS events primarily using the head-up tilt table testing model. In this regard, the most consistent finding is a marked increase in epinephrine (Epi) spillover into the circulation beginning at an early stage as VVS evolves. Reported alterations of circulating norepinephrine (NE), on the other hand, have been more variable. Plasma concentrations of other vasoactive agents have been reported to exhibit more variable changes during a VVS event, and for the most part change somewhat later, but in some instances the changes are quite marked. The neurohormones that have drawn the most attention include arginine vasopressin [AVP], adrenomedullin, to a lesser extent brain and atrial natriuretic peptides (BNP, ANP), opioids, endothelin-1 (ET-1) and serotonin. However, whether some or all of these diverse agents contribute directly to VVS pathophysiology or are principally a compensatory response to an evolving hemodynamic crisis is as yet uncertain. The goal of this communication is to summarize key reported neurohumoral findings in VVS, and endeavor to ascertain how they may contribute to observed hemodynamic alterations during VVS.

Original languageEnglish (US)
Article number76
JournalFrontiers in Cardiovascular Medicine
StatePublished - May 6 2020

Bibliographical note

Funding Information:
Funding. DB was supported in part by a philanthropic grant from the Dr. Earl E. Bakken family in support of heart-brain research.

Publisher Copyright:
© Copyright © 2020 Benditt, van Dijk, Krishnappa, Adkisson and Sakaguchi.


  • catecholamines
  • neuroendocrine
  • neurohormone
  • tilt-table testing
  • vasovagal syncope


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