Evidence that remodeling of insular cortex neurovascular unit contributes to
hypertension-related sympathoexcitation
#MMPMID28270592
Marins FR
; Iddings JA
; Fontes MA
; Filosa JA
Physiol Rep
2017[Mar]; 5
(5
): ? PMID28270592
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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 NMDA into intermediate IC of SHR evoked higher amplitude responses
of RSNA, MAP, and HR On the other hand, NMDA receptor blockade decreased baseline
RSNA, MAP and HR in SHR, with no changes in WKY Immunofluorescence data from SHR
intermediate IC showed increased NMDA receptor density, contributing to the SHR
enhanced sympathetic responses, and increased in vascular density (increased
number of branches and endpoints, reduced average branch length), suggesting
angiogenesis. Additionally, IC from SHR presented increased GFAP immunoreactivity
and contact between astrocyte processes and blood vessels. In SHR, 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 SHR is
accompanied by marked alterations to the NVU within the IC and enhanced
NMDA-mediated sympathoexcitatory responses likely contributors of the maintenance
of hypertension.
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