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Stress-Induced Susceptibility to Sudden Cardiac Death in Mice with Altered Serotonin Homeostasis
- Source :
- PLoS ONE, PLoS ONE, Vol 7, Iss 7, p e41184 (2012)
- Publication Year :
- 2012
- Publisher :
- Public Library of Science (PLoS), 2012.
-
Abstract
- In humans, chronic stressors have long been linked to cardiac morbidity. Altered serotonergic neurotransmission may represent a crucial pathophysiological mechanism mediating stress-induced cardiac disturbances. Here, we evaluated the physiological role of serotonin (5-HT) 1A receptors in the autonomic regulation of cardiac function under acute and chronic stress conditions, using 5-HT(1A) receptor knockout mice (KOs). When exposed to acute stressors, KO mice displayed a higher tachycardic stress response and a larger reduction of vagal modulation of heart rate than wild type counterparts (WTs). During a protocol of chronic psychosocial stress, 6 out of 22 (27%) KOs died from cardiac arrest. Close to death, they displayed a severe bradycardia, a lengthening of cardiac interval (P wave, PQ and QRS) duration, a notched QRS complex and a profound hypothermia. In the same period, the remaining knockouts exhibited higher values of heart rate than WTs during both light and dark phases of the diurnal rhythm. At sacrifice, KO mice showed a larger expression of cardiac muscarinic receptors (M2), whereas they did not differ for gross cardiac anatomy and the amount of myocardial fibrosis compared to WTs. This study demonstrates that chronic genetic loss of 5-HT(1A) receptors is detrimental for cardiovascular health, by intensifying acute, stress-induced heart rate rises and increasing the susceptibility to sudden cardiac death in mice undergoing chronic stress.
- Subjects :
- Male
Time Factors
Anatomy and Physiology
Mouse
lcsh:Medicine
Arrhythmias
030204 cardiovascular system & hematology
Cardiovascular
Cardiovascular System
Sudden cardiac death
Electrocardiography
Mice
0302 clinical medicine
Integrative Physiology
Homeostasis
Psychology
Chronic stress
lcsh:Science
Mice, Knockout
Multidisciplinary
Behavior, Animal
Experimental Psychology
Animal Models
Neurotransmitters
Electrophysiology
Mental Health
Receptor, Serotonin, 5-HT1A
cardiovascular system
Medicine
medicine.symptom
Research Article
Cardiac function curve
Bradycardia
Serotonin
medicine.medical_specialty
Heart Ventricles
Psychological Stress
Biology
Serotonergic
03 medical and health sciences
Model Organisms
Internal medicine
Heart rate
medicine
Animals
Social Behavior
5-HT receptor
Behavior
Models, Statistical
Acute Cardiovascular Problems
lcsh:R
Serotonin 5-HT1 Receptor Agonists
medicine.disease
Fibrosis
Mice, Inbred C57BL
Death, Sudden, Cardiac
Endocrinology
lcsh:Q
Physiological Processes
Stress, Psychological
030217 neurology & neurosurgery
Neuroscience
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....3887fb0f511d4468e6e3023c47603950