title: Evidence that remodeling of insular cortex neurovascular unit contributes to hypertension-related sympathoexcitation.
abstract: 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.
authors.affiliation: Departamento de Fisiologia e Biofísica, INCT, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Fernanda R
authors.initials: FR
authors.lastname: Marins
authors.affiliation: Department of Physiology, Augusta University, Augusta, Georgia.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Iddings
authors.affiliation: Departamento de Fisiologia e Biofísica, INCT, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Marco A P
authors.initials: MA
authors.lastname: Fontes
authors.affiliation: Department of Physiology, Augusta University, Augusta, Georgia jfilosa@augusta.edu.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Filosa
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects / Q000502:physiology; D001253:Astrocytes / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology*; D007668:Kidney / Q000294:innervation*; D016202:N-Methylaspartate / Q000494:pharmacology; D000069336:Neurovascular Coupling / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
chemical_list: D018690:Excitatory Amino Acid Agonists; D005904:Glial Fibrillary Acidic Protein; D016202:N-Methylaspartate
keywords: Hypertension; Insular cortex (IC); NMDA receptors; neurovascular unit (NVU)