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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 type:Scholarships in Brazil - Doctorate
Effective date (Start): December 01, 2016
Effective date (End): May 31, 2020
Field of knowledge:Biological Sciences - Physiology - General Physiology
Principal Investigator:Vagner Roberto Antunes
Grantee:Renato Willian Martins Sá
Home 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