Modulation of sympathetic activity by corticotropin-releasing hormone and atrial natriuretic peptide

Abstract

Background: Heart rate variability represents a reliable marker to delineate the status of autonomic nervous system (ANS) function and alterations due to stress in vivo. Interestingly, up to now the effects of corticotropin-releasing hormone (CRH), a key regulator of the stress hormone system, upon heart rate variability are not sufficiently described. Hence, we attempted to investigate the ANS-effects of a CRH bolus and the modulatory influences of atrial natriuretic peptide (ANP), one of the most important functional antagonist of CRH actions.

Methods: 12 healthy male volunteers were administered 100 microg CRH as bolus injection at 15:00. Six randomly chosen subjects received 150 microg ANP dissolved in normal saline and six subjects a normal saline infusion from 14:45 to 15:15. From 13:00 to 17:00 an ECG was recorded and mean heart rate (HR), total power (TP), very low frequency (VLF), low frequency (LF), LF in normalized units (LF [nu]), high frequency (HF) domains and the LF/HF-ratio in the interval from 14:00 to 16:00 were determined.

Results: After administration of CRH a significant increase in HR and a fast reduction of TP were observed, which lasted about 1 h. Based upon spectral domain analyses the sympathetic activity after CRH administration as indicated by LF [nu] increased by 31% (mean location) during saline. Applying ANP this increase was reduced to 19% (mean location). The VLF component, which is considered to be based in part also on sympathetic influences, indicates comparable effect. During saline the VLF after CRH bolus remained largely unchanged, but was reduced to 66% by ANP. Though the vagal activity indicated by the HF component was reduced after CRH, no significant differences emerged between both treatments. The changes of the LF/HF-ratio were pronounced in both groups. During saline this ratio increased by about 111%, during ANP only by 43% (mean location).

Conclusions: Based upon HRV analysis the CRH administration induced sympathotonic effects which were antagonized by ANP. The observed vagal changes were less pronounced and need further investigation. Further studies of autonomic effects by alterations of CRH secretion in depression and anxiety disorder are strongly warranted.