Salt-loading promotes extracellular ATP release mediated by glial cells in the hypothalamic paraventricular nucleus of rats

Autor(es)

Sa, Renato W. Martins ; Theparambil, Shefeeq M. ; dos Santos, Karoline Martins ; Christie, Isabel N. ; Marina, Nephtali ; Cardoso, Barbara V. ; Hosford, Patrick S. ; Antunes, Vagner R.

• Tipo de documento: Artigo Científico
• Fonte: Molecular and Cellular Neuroscience; v. 124, p. 9-pg., 2023-01-18.

Resumo

Previously, we have shown that purinergic signalling is involved in the control of hyperosmotic-induced sym-pathoexcitation at the level of the PVN, via activation of P2X receptors. However, the source(s) of ATP that drives osmotically-induced increases in sympathetic outflow remained undetermined. Here, we tested the two competing hypotheses that either (1) higher extracellular ATP in PVN during salt loading (SL) is a result of a failure of ectonucleotidases to metabolize ATP; and/or (2) SL can stimulate PVN astrocytes to release ATP. Rats were salt loaded with a 2 % NaCl solution replacing drinking water up to 4 days, an experimental model known to cause a gradual increase in blood pressure and plasma osmolarity. Immunohistochemical assessment of glial-fibrillary acidic protein (GFAP) revealed increased glial cell reactivity in the PVN of rats after 4 days of high salt exposure. ATP and adenosine release measurements via biosensors in hypothalamic slices showed that baseline ATP release was increased 17-fold in the PVN while adenosine remained unchanged. Disruption of Ca2+- dependent vesicular release mechanisms in PVN astrocytes by virally-driven expression of a dominant-negative SNARE protein decreased the release of ATP. The activity of ectonucleotidases quantified in vitro by production of adenosine from ATP was increased in SL group. Our results showed that SL stimulates the release of ATP in the PVN, at least in part, from glial cells by a vesicle-mediated route and likely contributes to the neural control of circulation during osmotic challenges. (AU)

• Processo FAPESP: 19/19894-8 - Caracterização neuroanatômica e funcional da sinalização purinérgica em núcleos hipotalâmicos envolvidos no controle de fluidos corpóreos e hipertensão neurogênica decorrente da alta ingestão de sal
• Beneficiário: Vagner Roberto Antunes
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/21991-3 - Hipertensão secundária à alta ingestão de sal: estudo da sinalização purinérgica em células neuronais do hipotálamo e sua influência na atividade do sistema nervoso autônomo e pressão arterial
• Beneficiário: Vagner Roberto Antunes
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/03359-8 - Estudo do papel da glia e ectonucleotidases na sinalização purinérgica do núcleo paraventricular do hipotálamo na hipertensão induzida por sal
• Beneficiário: Renato Willian Martins Sá
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 18/19907-0 - Interferência gênica em neurônios do núcleo motor dorsal do vago e sua influência nas disfunções autonômicas de animais espontaneamente hipertensos
• Beneficiário: Karoline Martins dos Santos
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto