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

Author(s)

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.

• Document type: Journal article
• Source: Molecular and Cellular Neuroscience; v. 124, p. 9-pg., 2023-01-18.

Abstract

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)

• FAPESP's process: 19/19894-8 - Neuroanatomical and functional identification of the purinergic signaling in hypothalamic nuclei involved in the control of body fluids and salt-induced hypertension
• Grantee: Vagner Roberto Antunes
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/21991-3 - Salt-induced hypertension: role of purinergic signaling in the neuronal cells at the hypothalamus level, and its correlation with the autonomic nervous system and blood pressure control
• Grantee: Vagner Roberto Antunes
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/03359-8 - Role of glia and ectonucleotidases in the purinergic signaling of the paraventricular nucleus of the hypothalamus in salt-induced hypertension
• Grantee: Renato Willian Martins Sá
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/19907-0 - Gene interference on the dorsol motor of vagus neurons and its influence on the autonomic dysfunctions of spontaneously hypertensive rats
• Grantee: Karoline Martins dos Santos
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)