Hypoperfusion/Hypoxia-Induced Oxytocin Neuronal Activation Following Acute Myocardial Infarction

Myocardial infarction (MI) is a leading cause of mortality, with post-MI cardiac arrhythmias, driven in part by heightened central neurohumoral activation—being major contributors. We previously showed that oxytocin (OT) neurons in the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei are activated following MI, and that central OT receptor (OTR) blockade suppresses MI-induced sympathetic outflow, reducing arrhythmias and mortality. However, the mechanisms driving this OT neuronal activation remain unknown. Given evidence for reduced cerebral blood flow (CBF) post-MI and for hypoxia-induced SON/PVN OT neuron activation, we hypothesized that acute MI causes hypoperfusion/hypoxia in SON/PVN, driving OT neuronal activation and somatodendritic OT release that may promote arrhythmogenesis. Using a rat model of ischemic MI and a novel transpharyngeal approach enabling in vivo two-photon imaging of SON, we measured parenchymal artery (PA) diameter, blood flow, and pO 2 before and after MI, alongside mean arterial pressure (MAP), heart rate (HR), and arrhythmias. At 30 min post-MI, MAP decreased while HR increased by ~20mmHg and ~30BPM, respectively (n=5, p< 0.01, paired t-est, for both MAP and HR). MI significantly reduced PA blood flow (n=4, p< 0.01, One-way ANOVA) and SON pO 2 (n=5, p< 0.001, One-way ANOVA), with appearance of arrhythmic episodes. To test whether hypoxia increases OT neuronal activity, we performed ex-vivo electrophysiological recording from OT neurons during transient hypoxia (20% pO 2 ) and found elevated firing frequency compared to normoxia (95% pO 2 ) (0.91±0.57 Hz vs. 1.51±0.78 Hz, n=5, p< 0.001, paired t-test). OT neuronal excitability was also enhanced in rats 7 days post-MI compared to sham (n=5/group, p< 0.01, paired t-test). To assess whether MI-induced OT activation affects local vascular tone, we locally applied OT (1mM) via microdialysis, which induced PA vasoconstriction (n=4, p< 0.05, One-way ANOVA). Similar vasoconstriction occurred 30–90 min following MI (n=3, p< 0.05, One-way ANOVA) and was prevented by OTR antagonist (200mM) (n=2 limits statistical significance at this point). Together, these findings indicate that acute MI induces hypoperfusion/hypoxia in SON, driving OT neuronal activation and associated PA vasoconstriction, suggesting somatodendritic OT release. The role of this local OT signaling in neurohormonal activation and arrhythmia generation remains to be determined. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.