Role of glia and ectonucleotidases in the purinergic signaling of the paraventricular nucleus of the hypothalamus in salt-induced hypertension

• Grant number: 16/03359-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2016
• End date: May 31, 2020
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Vagner Roberto Antunes
• Grantee: Renato Willian Martins Sá
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 18/11203-3 - Purinergic signalling in neuron-glia interactions at the PVN level during osmotic challenges, BE.EP.DR

Abstract

Hyperosmolality is an imbalance of homeostatic control of osmolality mainly due to an elevation of the sodium concentration in the extracellular milieu. It is well established that increasing in osmolality, due to a salt loading, leads to rise in the blood pressure associated to a simpathoexcitation at the PVN neuronal level. Recent observations from our laboratory have shown that ATP, acting on P2 receptors at the PVN level, is involved in hyperosmolality-induced sympathoexcitation. Thus, here we hypothesize that hyperosmolality-induced hypertension and sympathoexcitation of salt-loaded animals relay on the activation of purinergic signaling due to an imbalance between ATP availability from glial cells and/or a reduction of ectonucleotidases expression that failure to breakdown ATP at the PVN neuronal environment. To test our hypothesis we are going to use 2 cohorts of male Wistar rats (280-320 g): i) normohydrated (tap water); ii) salt-loaded animals with hypertonic solution (NaCl 2%) in replacement of the tap water for 7 days. ATP release will be measured in real time using a biossensor placed into PVN. To evaluate the role of glial cells as the source of ATP release, primary neuronal culture of hypothalamic cells will be stimulated by hypertonic saline (300, 400, 500 and 600 mOsmol/kgH2O) in the presence fluoroacetate (1mM). In order to interfere with ATP-mediated signaling by promoting facilitated breakdown of extracellular ATP, a lentiviral vector LVV-EF1a-TMPAP-EGFP will be used to drive the expression of TMPAP in radiotelemetered animal for blood pressure and heart rate recording

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

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.. Salt-loading promotes extracellular ATP release mediated by glial cells in the hypothalamic paraventricular nucleus of rats. Molecular and Cellular Neuroscience, v. 124, p. 9-pg., 2023-01-18. (19/19894-8, 16/21991-3, 16/03359-8, 18/19907-0)

GOMES, PAULA MAGALHAES; BATISTA, JULIA SANTOS; SA, RENATO WILLIAN MARTINS; ANTUNES, VAGNER ROBERTO. Short exposure to high salt in drinking solution leads to a cardiovascular phenotype of hypertension without changes in the blood volume of rats. Experimental Physiology, v. N/A, p. 10-pg., 2023-01-30. (16/03359-8, 19/19894-8, 19/23588-0)

SA, RENATO WILLIAN MARTINS; RIBEIRO, NATALIA; RIBEIRO, LUCIENE MARIA; MENDONCA, JOHNNY MENDES; SANTOS, KAROL MARTINS; ANTUNES, VAGNER ROBERTO. Ectonucleotidases in the Hypothalamus of Salt-Induced Hypertensive Rats: Transcriptional Profile and functional implications. FASEB JOURNAL, v. 32, n. 1, p. 2-pg., 2018-04-01. (16/21991-3, 16/03359-8)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SÁ, Renato Willian Martins. Role of astrocytes and ectonucleotidases in purinergic signaling of the paraventricular nucleus of hypothalamus in salt-induced hypertension.. 2020. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.