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

Impaired serotonergic regulation of heart rate may underlie reduced baroreflex sensitivity in an... 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. serotonin-1A receptors; 8-hydroxy-2-(di- n -propylamino)tetralin; Flinders Sensitive Line rat; vagus; telemetry Address for reprint requests and other correspondence: A. K. Goodchild, Australian School of Advanced Medicine, Level 1 Dow Corning Bldg. Macquarie Univ., Sydney, Australia (e-mail: ann.goodchild@vc.mq.edu.au ) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Heart and Circulatory Physiology The American Physiological Society

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

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References (56)

Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0363-6135
eISSN
1522-1539
DOI
10.1152/ajpheart.01009.2007
pmid
17993598
Publisher site
See Article on Publisher Site

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. serotonin-1A receptors; 8-hydroxy-2-(di- n -propylamino)tetralin; Flinders Sensitive Line rat; vagus; telemetry Address for reprint requests and other correspondence: A. K. Goodchild, Australian School of Advanced Medicine, Level 1 Dow Corning Bldg. Macquarie Univ., Sydney, Australia (e-mail: ann.goodchild@vc.mq.edu.au )

Journal

AJP - Heart and Circulatory PhysiologyThe American Physiological Society

Published: Jan 1, 2008

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