Abstract
Myocardial infarction (MI) initiates an increase in cardiac sympathetic nerve activity (SNA) that facilitates potentially fatal arrhythmias. The mechanism(s) underpinning sympathetic activation remain unclear. Some neuronal populations within the hypothalamic paraventricular nucleus (PVN) have been implicated in SNA. This study elucidated the role of the PVN in triggering cardiac SNA following MI (left anterior descending coronary artery ligation). By means of c-Fos, oxytocin, and vasopressin immunohistochemistry accompanied by retrograde tracing we showed that MI activates parvocellular oxytocin neurons projecting to the rostral ventral lateral medulla. Central inhibition of oxytocin receptors using atosiban (4.5 µg in 5 µl, i.c.v.), or retosiban (3 mg/kg, i.v.), prevented the MI-induced increase in SNA and reduced the incidence of ventricular arrhythmias and mortality. In conclusion, pre-autonomic oxytocin neurons can drive the increase in cardiac SNA following MI and peripheral administration of an oxytocin receptor blocker could be a plausible therapeutic strategy to improve outcomes for MI patients.
Highlights
Myocardial infarction (MI) initiates an increase in cardiac sympathetic nerve activity (SNA) that facilitates potentially fatal arrhythmias
In this series of experiments, we again observed a higher number of c-Fos-positive neurons in the parvocellular PVN (pPVN) of MI rats compared to sham rats (Fig. 2a–c)
There appeared to be a higher number of oxytocin-positive neurons in the pPVN of MI rats compared to sham rats, it was not significant (Fig. 2d)
Summary
Myocardial infarction (MI) initiates an increase in cardiac sympathetic nerve activity (SNA) that facilitates potentially fatal arrhythmias. The initial increase in cardiac SNA within the first hours following MI is known to contribute, at least in part, to the generation of ventricular arrhythmias[1,2], which is responsible for sudden heart failure and death[3]. Once established, this sympathetic hyper-excitation is essentially irreversible and facilitates permanent structural and functional damage of the heart[4]. A distinct subpopulation of pre-autonomic neurons (some of which release oxytocin or vasopressin) project to the rVLM16–18 and have been implicated in the modulation of SNA17,19
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.
