Abstract P412: Microglia Via P2y 12 Transmit Hemodynamic Signal To Promote Sympathetic Activation In Hypertension

Abstract

Hypertension is characterized by elevated sympathetic tonicity, but how sympathetic hyperactivity is triggered is not fully understood. Recent studies reveal that microglia highly involve in the regulation of sympathetic neuronal activity in the hypothalamic paraventricular nucleus (PVN). In this study, we performed a temporospatial analysis of microglia at both morphological and transcriptomic levels, and found that microglia in the PVN were the earliest responders to hypertensive challenge. Comprehensive vasculature analysis unveiled that PVN was characterized by high capillary density, thin vessel diameter, and complex vascular topology compared to other brain regions. PVN is susceptible to the penetration of ATP derived from the vasculature in response to hemodynamic disturbance upon pressor challenge. Furthermore, either pharmacological blockade or genetic ablation of microglia P2Y12 could substantially restrain pressor response under hypertensive stimulation Together, these findings suggest that a unique vasculature pattern endows PVN with susceptibility to hypertension-associated hemodynamic insults, which is mediated by microglia.