Dados do Trabalho

Título

Angiotensin II, blood-brain barrier and microglia association during the transition from pre- to hypertensive phase

Introdução

Chronic hypertension is characterized by upregulation of the renin-angiotensin system, increased blood-brain barrier (BBB) permeability and microglia activation within autonomic nuclei, and an intense sympathoexcitation. There is no information on the interplay of these events during the development of neurogenic hypertension.

Objetivo

We identified the interaction and time-course chances of AngII availability, BBB dysfunction, microglia activation and autonomic imbalance within autonomic areas of young SHR and Wistar rats.

Método

Hemodynamic/autonomic parameters, BBB permeability, microglia structure/density and AngII expression were evaluated within the paraventricular hypothalamic nucleus, nucleus of solitary tract and rostral ventrolateral medulla in rats aged 4, 5, 6, 8 and 12 weeks old.

Resultados

Augmented brain AngII expression (5th week) was the first observed change followed by the incipient BBB leakage and microglia activation (6th week). From the 6th to 12th week BBB permeability increased continuously adding leaked plasma to locally synthesized AngII, the augmented peptide content strongly activated microglial cells within autonomic nuclei thus driving the hemodynamic (blood pressure elevation, heart rate reduction) and autonomic responses (increased sympathetic vasomotor activity modulation and pressure viability) that occurred from the 8th week on. Augmented local AngII availability was able to colocalize with the microglial cells and alter their morphologic phenotype from highly ramified cells, suggestive of a basal surveillant condition (4th-5th week) to short process arbors, fewer ramifications and enlarged soma size in the chronic phase, characteristic of the secretory phenotype. These responses were not specific for autonomic nuclei also occurring with smaller magnitude in the somatosensory cortex and hypoglossal nucleus, indicating the predominance of hypertension-induced effects on autonomic areas. No changes were observed in age-matched controls where AngII density does not change.

Conclusão

Brain-synthesized AngII is the initial stimulus to drive coordinated BBB permeability changes and microglial activation. BBB leakage activates a vicious cycle in which augmented brain AngII availability further potentiates barrier permeability, microglial activation, autonomic imbalance and pressure elevation during the establishment of hypertension. Financial support: FAPESP; CAPES.