Evidence that remodeling of insular cortex neurovascular unit contributes to hypertension‐related sympathoexcitation

摘要

The intermediate region of the posterior insular cortex (intermediate IC) mediates sympathoexcitatory responses to the heart and kidneys. Previous studies support hypertension‐evoked changes to the structure and function of neurons, blood vessels, astrocytes and microglia, disrupting the organization of the neurovascular unit (NVU). In this study, we evaluated the functional and anatomical integrity of the NVU at the intermediate IC in the spontaneously hypertensive rat (SHR) and its control the Wistar‐Kyoto (WKY). Under urethane anesthesia, NMDA microinjection (0.2 mmol/L/100 nL) was performed at the intermediate IC with simultaneous recording of renal sympathetic nerve activity (RSNA), heart rate (HR) and mean arterial pressure (MAP). Alterations in NVU structure were investigated by immunofluorescence for NMDA receptors (NR1), blood vessels (70 kDa FITC‐dextran), astrocytes (GFAP), and microglia (Iba1). Injections of style="fixed-case">NMDA into intermediate style="fixed-case">IC of style="fixed-case">SHR evoked higher amplitude responses of style="fixed-case">RSNA, style="fixed-case"> MAP, and style="fixed-case">HR. On the other hand, style="fixed-case">NMDA receptor blockade decreased baseline style="fixed-case">RSNA, style="fixed-case"> MAP and style="fixed-case">HR in style="fixed-case">SHR, with no changes in style="fixed-case">WKY. Immunofluorescence data from style="fixed-case">SHR intermediate style="fixed-case">IC showed increased style="fixed-case">NMDA receptor density, contributing to the style="fixed-case">SHR enhanced sympathetic responses, and increased in vascular density (increased number of branches and endpoints, reduced average branch length), suggesting angiogenesis. Additionally, style="fixed-case">IC from style="fixed-case">SHR presented increased style="fixed-case">GFAP immunoreactivity and contact between astrocyte processes and blood vessels. In style="fixed-case">SHR, style="fixed-case"> IC microglia skeleton analysis supports their activation (reduced number of branches, junctions, endpoints and process length), suggesting an inflammatory process in this region. These findings indicate that neurogenic hypertension in style="fixed-case">SHR is accompanied by marked alterations to the style="fixed-case">NVU within the style="fixed-case">IC and enhanced style="fixed-case">NMDA‐mediated sympathoexcitatory responses likely contributors of the maintenance of hypertension.