Abstract
Cardiovascular disease remains the leading cause of mortality in New Zealand, responsible for almost one third of all deaths. Myocardial infarction (MI), the occlusion of a major coronary artery, commonly referred to as a “heart attack”, represents the most severe manifestation of coronary artery disease. This acute ischemic event not only damages myocardium, but triggers neurohormonal and autonomic activity, contributing to the progression of ongoing complications. This autonomic activity includes heightened sympathetic nervous system activity, which has been known for decades, however the underlying mechanisms driving this response remain poorly understood. The Paraventricular Nucleus (PVN) of the hypothalamus is a critical integrative centre of the brain, containing diverse neuronal populations that synthesize various neuropeptides, including oxytocin and arginine-vasopressin. In recent years, the PVN has emerged as a key regulator of autonomic outflow. Evidence suggests oxytocin neurons within the hypothalamic PVN contribute to mediating the elevated cardiac sympathetic nerve activity (cSNA) in the acute phase following MI. With those able to survive the MI still facing severe complications and disability for the rest of their lives, looking at the potential role of these neurons in the chronic setting was crucial.
This project investigated the role of oxytocin and vasopressin neurons within the hypothalamic PVN in sustaining the chronic elevation of cardiac SNA following acute MI. Animals were grouped according to left ventricular free wall infarct size. Immunohistochemistry experimentation revealed a negative correlation between infarct size and chronic oxytocin and vasopressin neuronal activation four weeks post MI. In vivo fibre photometry carried out on oxytocin-Cre mice allowed real-time, high temporal recordings to demonstrate the effect of vocal stress, exclusively on oxytocin neuronal activity at designated time points. Analysis of oxytocin neuron activation in response to the stressor detected minimal significant differences between groups due to large variation. These findings provide novel insight into the central mechanisms involved in the sustained elevated cSNA following acute MI. This highlights that in contrast to the acute setting, oxytocin and vasopressin neuronal activation appear to be down regulated in the chronic setting. While further research is required to determine the precise mechanisms involved in the sustained increase in cardiac SNA, a potential mechanism may involve corticotropin-releasing hormone (CRH) neurons in the PVN. CRH neurons are known to have a major role in regulating the hypothalamic-pituitary-adrenal axis and the stress response.