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-HT1A 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-HT1A 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.
Highlights
In humans, there is broad and unequivocal evidence of causative association between chronic psycho-emotional stress and cardiovascular disorders, including myocardial ischemia and sudden cardiac death [1,2]
We investigated whether 5-HT1A KO mice were less protected at the level of the heart when exposed to chronic psychosocial stress (CPS)
In wild type counterparts (WTs) the increase in heart rate associated with drug administration reverted to the basal level within 7 min, whereas KO mice showed a much slower recovery of HR values towards basal level (Figure 2A)
Summary
There is broad and unequivocal evidence of causative association between chronic psycho-emotional stress and cardiovascular disorders, including myocardial ischemia and sudden cardiac death [1,2]. The neurotransmitter serotonin (5-HT) has been implicated in the control of cardiovascular function during stress, and a large body of experimental evidence regarding its site of action, receptor types and underlying mechanisms has been generated (see [5] for a comprehensive review). It appears that, among at least 14 subtypes of 5-HT receptors, it is the 5-HT-1A (5-HT1A) subtype receptor whose involvement in cardiac control during stress is best documented. With this finding, exogenous activation of these receptors via systemic administration of 5-HT1A agonists attenuates stress-induced tachycardic response to various psychological stressors in rats and rabbits [13,14,15]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
