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Psychoneuroendocrinology. 2019 Apr;102:196-203. doi: 10.1016/j.psyneuen.2018.12.017. Epub 2018 Dec 14.

Vagal effects of endocrine HPA axis challenges on resting autonomic activity assessed by heart rate variability measures in healthy humans.

Author information

1
Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, D-20246, Hamburg, Germany; Department of Psychiatry, Division of Neurosciences, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, GR-54124, Thessaloniki, Greece. Electronic address: aagorastos@uke.uni-hamburg.de.
2
Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, D-20246, Hamburg, Germany.
3
Center for Neurogenomics and Cognitive Research, VU University Amsterdam, NL-1081, HV, Amsterdam, the Netherlands; Department of Health, Safety and Environment, VU University Amsterdam, NL-1081, BT, Amsterdam, the Netherlands.
4
Center for Neurogenomics and Cognitive Research, VU University Amsterdam, NL-1081, HV, Amsterdam, the Netherlands.
5
School of Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, NL-6200 MD, Maastricht, the Netherlands.

Abstract

BACKGROUND:

The hypothalamic-pituitary-adrenal axis (HPA axis) and the autonomic nervous system (ANS) are considered to play the most crucial role in the pathophysiology of stress responsiveness and are increasingly studied together. However, only few studies have simultaneously assessed HPA axis and ANS activity to investigate their direct interaction in pathophysiology, while no study so far has assessed the dynamic interplay between the two systems in healthy subjects through endocrine challenges.

METHODS:

The present study assessed the direct effects of overnight pharmacoendocrine HPA axis challenges with dexamethasone (suppression) and metyrapone (stimulation) on ANS activity at rest as determined by linear and nonlinear measures of heart rate variability (HRV) in 39 young healthy individuals.

RESULTS:

Findings indicated significant effects of metyrapone, but not dexamethasone on autonomic activity at rest based on HRV measures. HRV after metyrapone was overall significantly reduced in comparison to baseline or post-dexamethasone conditions, while the combined metyrapone-related reduction of HRV measures RMSSD, NN50(%) and HF(%) with concomitant increase of the unifractal scaling coefficient αfast value jointly indicated a specifically diminished vagal activity.

CONCLUSIONS:

We provide first data that HPA axis stimulation (metyrapone) is associated with reduced vagal tone, while HPA axis suppression (dexamethasone) has no effect on autonomic modulation of heart function. Our results support a vital role of the parasympathetic nervous system in the interplay between ANS and HPA axis and, thus, in the modulation of stress-related cardiovascular responsiveness and the susceptibility to stress-related disorders.

KEYWORDS:

Autonomic nervous system; Cortisol; Dexamethasone; Endocrine challenge; Heart rate variability; Hypothalamus-pituitary-adrenal axis (HPA axis); Metyrapone; Stress; Vagus

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