Article

Impaired serotonergic regulation of heart rate may underlie reduced baroreflex sensitivity in an animal model of depression.

Australian School of Advanced Medicine, Macquarie University, Sydney, Australia.
AJP Heart and Circulatory Physiology (impact factor: 3.71). 02/2008; 294(1):H474-80. DOI:10.1152/ajpheart.01009.2007 pp.H474-80
Source: PubMed

ABSTRACT Serotonin (5-HT) is crucial to normal reflex vagal modulation of heart rate (HR). Reduced baroreflex sensitivity [spontaneous baroreflex sensitivity (sBRS)] and HR variability (HRV) reflect impaired neural, particularly vagal, control of HR and are independently associated with depression. In conscious, telemetered Flinders-Sensitive Line (FSL) rats, a well-validated animal model of depression, we tested the hypothesis that cardiovascular regulatory abnormalities are present and associated with deficient serotonergic control of reflex cardiovagal function. In FSL rats and control Flinders-Resistant (FRL) and Sprague-Dawley (SD) rat strains, diurnal measurements of HR, arterial pressure (AP), activity, sBRS, and HRV were made. All strains had normal and similar diurnal variations in HR, AP, and activity. In FRL rats, HR was elevated, contributing to the reduced HRV and sBRS in this strain. In FSL rats, sBRS and high-frequency power HRV were reduced during the night, indicating reduced reflex cardiovagal activity. The ratio of low- to high-frequency bands of HRV was increased in FSL rats, suggesting a relative predominance of cardiac sympathetic and/or reflex activity compared with FRL and SD rats. These data show that conscious FSL rats have cardiovascular regulatory abnormalities similar to depressed humans. Acute changes in HR, AP, temperature, and sBRS in response to 8-hydroxy-2-(di-n-propylamino)tetralin, a 5-HT(1A), 5-HT(1B), and 5-HT(7) receptor agonist, were also determined. In FSL rats, despite inducing an exaggerated hypothermic effect, 8-hydroxy-2-(di-n-propylamino)tetralin did not decrease HR and AP or improve sBRS, suggesting impaired serotonergic neural control of cardiovagal activity. These data suggest that impaired serotonergic control of cardiac reflex function could be one mechanism linking reduced sBRS to increased cardiac risk in depression.

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Keywords

cardiac reflex function
 
cardiovascular regulatory abnormalities
 
conscious FSL rats
 
control Flinders-Resistant
 
deficient serotonergic control
 
depressed humans
 
exaggerated hypothermic effect
 
FRL rats
 
FSL rats
 
heart rate
 
high-frequency power HRV
 
HR variability
 
impaired serotonergic control
 
normal reflex vagal modulation
 
reduced HRV
 
reflex cardiovagal activity
 
reflex cardiovagal function
 
relative predominance
 
SD rats
 
serotonergic neural control